Effect of the interval between birth and second dose of hepatitis B vaccine on perinatal transmission of hepatitis B virus.

Preventing perinatal transmission is important for hepatitis B (HepB) elimination. We conducted a retrospective cohort study to assess the interval between HepB birth-dose (HepB-BD) to second-dose (HepB-SD) vaccination on perinatal transmission. Among 39,313 infants born to HepB s-antigen (HBsAg)-positive mothers from a Korean national database 38,411 (97.7%) had completed timely immunophylaxis with HepB-BD 41,572 (99.8%) with hepatitis B immune globulin, and 1027 (2.6%) were HBsAg-positive at ≥ 9 months. Maternal factors (i.e. HepB e-antigen status, age, or nationality) were associated with an increased risk of infection whereas short gestational length decreased it. The HepB-BD - HepB-SD interval (<8 vs. ≥8 weeks) did not alter the risk.

High coverage and timeliness of vaccination of children under 6 years of age in Risaralda, Colombia.

This study determined the coverage and timeliness of immunization in children <6 y from Risaralda, Colombia. A retrospective cross-sectional study evaluated data from a vaccination coverage and timeliness verification survey conducted in 2019, including 2457 children <6 y from Risaralda, Colombia. Variables included demographics, a record of vaccinations included in the Colombian Vaccination Plan, and date of immunization. Vaccination was defined as timely until 29 d after the day established by the plan. Coverage was over 95% for all vaccinations, except the boosters of diphtheria/pertussis/tetanus (DTP) and oral polio at 18 months (91.0%), influenza (85.6%), and yellow fever (49.2%). Most surveyed children demonstrated very high timeliness of vaccination, with values close to, or over, 90%, although there were exceptions for pentavalent (DTP+Haemophilus influenzae type B+hepatitis B) and polio vaccines at 6 months (79.4%), influenza (85.6%), and yellow fever (49.2%). Before the COVID-19 pandemic, Colombian Vaccination Plan demonstrated high coverage and timeliness of vaccination of children <6 y of age; however, timeliness for the third dose of DTP-Hib-HBV and polio showed opportunities for improvement.

Pertussis in Mexico from 2000 to 2019: A real-world study of incidence, vaccination coverage, and vaccine effectiveness.

BACKGROUND: The national immunization program in Mexico includes a 3-dose primary series of pertussis vaccine and a toddler booster dose. In Mexico, whole-cell pertussis vaccines (wP) were switched in 2007 to acellular pertussis vaccines (aP). METHODS: This retrospective study using Mexican National Databases of Health and population surveillance (2000-2019) assessed the incidence of pertussis, infant pertussis vaccination coverage, and vaccine effectiveness (VE) against clinically-diagnosed and/or laboratory-confirmed pertussis in children aged 6.5-18.5 or 24.5 months for the primary series, and children aged 18.5 or 24.5-48.5 months for the toddler booster. RESULTS: The incidence of pertussis sharply increased in 2012 and was highest in 2012, 2015, and 2016 (0.84-0.94/100,000 person-years). Coverage was highest for the first dose in the primary series, decreasing for each subsequent dose. The VE against notified pertussis was 96.4% (95% CI: 94.7, 97.6) for the first three doses of wP vaccine (2000-2007) and 95.7% (95% CI: 95.1, 96.2) for the first three doses of aP vaccine (2008-2019). CONCLUSIONS: Our findings suggested high levels of vaccine effectiveness overall were achieved for the aP and wP vaccines in Mexico between 2000 and 2019.

Infant vaccination against pertussis in Argentina: Parent-reported outcomes on reactogenicity, impact on daily routine and satisfaction after pentavalent whole-cell or hexavalent acellular pertussis vaccines.

Introduction: In Argentina, a pentavalent whole-cell pertussis vaccine (wP) is used in the National Immunization Program, however hexavalent acellular pertussis (aP) vaccines are available in the private market. Objective: To describe parent or guardians perceptions on reactogenicity, daily routine and satisfaction after a first or third dose of a wP-pentavalent plus IPV (wP-group) or the fully-liquid aP-hexavalent vaccine (aP-group) in infants. Material and methods: This was a prospective observational and analytical study. Parents or guardians of infants born at term attending a public or private vaccination center in Buenos Aires City were invited to participate. All parents or guardians had completed 12-year schooling and were asked to fill out an online 7-day post vaccination questionnaire. The questionnaire was validated as the first phase of the study. Descriptive analysis of study variables was carried out, REDCap was used for the online survey, and STATA 14 for data analysis. Results: 1071 parents or guardians answered the questionnaire (response rate 82%), 530 for wP-group and 541 for aP-group.Local and systemic adverse reactions, in groups wP and aP respectively, were: pain 83%, 28%; swelling 63%, 16%; redness 52%, 22%; irritability 72%, 52%; fever 37%, 8%; loss of appetite 36%, 19%; drowsiness 38%, 27%; and vomiting 15%, 11%.Impact on daily life: social activities 36%, 20%; routine 48%, 24%; mood 39%, 23%; vitality 47%, 24%; sleep 50%, 30%; and appetite 22%, 7%.Parents were satisfied with the vaccination process in 96% and 98% for wP-group and aP-group respectively. Parents reported willingness to bring infant for future vaccine doses in 97% and 99% for wP-group and aP-group respectively. Conclusions: Reported reactogenicity and impact on family daily routine was higher in infants receiving wP-pentavalent than aP-hexavalent vaccines. Parents in both groups conveyed vaccine acceptance and positive intentions for future immunizations.

Prenatal tetanus-diphtheria-acellular pertussis vaccine effectiveness at preventing infant pertussis.

OBJECTIVE: To evaluate the effectiveness of the tetanus, diphtheria, and acellular pertussis (Tdap) vaccine containing five pertussis components (Tdap5; Adacel®, Sanofi) when given during pregnancy at preventing pertussis in infants less than 2 months of age. METHODS: The US Centers for Disease Control and Prevention (CDC), in collaboration with the Emerging Infections Program (EIP) Network, undertook a case-control study evaluating the effectiveness of Tdap vaccination in pregnancy against pertussis in infants less than 2 months of age based on data collected by the EIP Network from 2011 through 2014. The dataset from the CDC/EIP Network study was used to conduct this product-specific vaccine effectiveness analysis of Tdap5 vaccination in pregnancy to prevent disease in young infants. The main outcome of interest was vaccine effectiveness in infants whose pregnant parents were vaccinated with Tdap5 between 27 and 36 weeks' gestation, in accordance with the ideal timing for Tdap vaccination in pregnancy recommended by the US Advisory Committee on Immunization Practices. Odd ratios (ORs) and 95 % confidence intervals (CIs) were estimated using conditional logistic regression, and vaccine effectiveness was calculated as (1-OR) × 100 %. RESULTS: There were 160 infant pertussis cases and 302 matched controls included in this Tdap5-specific study. Tdap5 effectiveness in preventing pertussis in infants whose pregnant parents were vaccinated between 27 and 36 weeks' gestation was 92.5 % (95 % CI, 38.5 %-99.1 %). Effectiveness of Tdap5 against pertussis-related hospitalization in infants whose pregnant parents were vaccinated between 27 and 36 weeks' gestation could not be calculated due to lack of discordance among matched cases and controls. Vaccination of the parents after pregnancy or less than 14 days before delivery did not protect infants from pertussis. CONCLUSIONS: Tdap5 vaccination in pregnancy between 27 and 36 weeks' gestation is highly effective at protecting young infants from pertussis. STUDY REGISTRATION: ClinicalTrials.gov, NCT05040802.

Ultrasound Criteria and Baker Scale for Breast Implant Capsular Contracture Diagnosis.

Due to the subjectivity of the Baker scale in grading capsular contracture (CC), an objective and reproducible measurement tool is necessary to estimate the presence and grade of CC in patients with breast implants. This study aimed to assess the capacity of breast ultrasonography to identify CCs using the Baker grading system. Methods: This study included patients who underwent breast augmentation with implants or implant-based breast reconstruction. Patient demographics, surgical type, and ultrasonographic variables were analyzed. The Kruskal-Wallis test was used to determine differences between means, and the Fisher exact test was used for binary variables. Results: A total of 21 patients (28 breasts) with smooth surface implants were included. In total, 39.2% of breasts had a score of Baker I, 25% had Baker II, 17.9% had Baker III, and 17.9% had Baker IV. When comparing breasts graded Baker I to IV, a mean capsule thickness of 0.6 ± 0.2, 1.0 ± 0.53, 1.68 ± 0.99, and 1.52 ± 0.46 mm, respectively, was shown (P = 0.0044). The breast implant deformity variable was significantly different between Baker grades I to IV (0.0218). Finally, Baker III and IV categories were five times more likely to have abnormal wrinkles than Baker I and II (odds ratio, 5.25; 95% confidence interval, 0.82-33.45; P = 0.0496). Conclusion: Ultrasound is a useful tool for evaluating the presence of augmented thickness, implant shape deformity, and abnormal wrinkles of the implant shell in correlation with the severity of CC.

Hepatitis B surface antigen prevalence and the rates of mother-to-child transmission of hepatitis B virus after the introduction of infant vaccination programs in South East Asia and Western Pacific regions: a systematic review.

OBJECTIVES: Infant vaccination against the hepatitis B virus began in the World Health Organization South East Asia Region and the Western Pacific Region between 1983 and 2016. This systematic review examined the seroprevalence of hepatitis B surface antigen (HBsAg) in children and the rate of mother-to-child transmission (MTCT) in these regions between 1990 and 2020. METHODS: MEDLINE and EMBASE were searched for articles published between January 1990 and September 2020, which reported seroprevalence of HBsAg in children aged 0-15 years and/or the rate of MTCT in the South East Asia Region and Western Pacific Region. A pragmatic review identified supporting information. This review was registered in the International Prospective Register of Systematic Reviews (#CRD42020211707). RESULTS: Of 115 included studies, 77 (24 countries) reported HBsAg prevalence, and 38 (nine countries) reported MTCT. The seroprevalence of HBsAg ranged between 0.0% and 27.4%, with a decreasing trend over time in each country. MTCT rates were 0.0-5.2% in infants of mothers who are hepatitis B e antigen-negative and 2.7-53.0% in infants of mothers who are hepatitis B e antigen-positive. CONCLUSION: After the introduction of infant hepatitis B virus vaccination programs, the countries in South East Asia Region and Western Pacific Region observed a reduction in HBsAg seroprevalence in children. Nevertheless, the risk of MTCT persists, emphasizing the importance of antenatal screening to identify high-risk pregnancies.

What is the true burden of diphtheria, tetanus, pertussis and poliovirus in children aged 3-18 years in Asia? A systematic literature review.

OBJECTIVES: In recent years, outbreaks and a rising incidence of diphtheria, tetanus, and pertussis have occurred in Asia, particularly in older children. METHODS: A systematic search of MEDLINE and Embase was conducted from January 2000 to October 2020 to identify the epidemiology of diphtheria, tetanus, pertussis, and poliomyelitis in children and adolescents (aged 3-18 years) in Asia. The results were then related to vaccination schedules, booster coverage rates, pertussis source of infection, and booster immunogenicity, as identified by a pragmatic review. The International Prospective Register of Systematic Reviews (PROSPERO) registration: #CRD42020222445. RESULTS: A total of 35 studies were included in this review. Limited data were reported on the epidemiology of diphtheria, tetanus, pertussis, and poliomyelitis. Data from studies reporting the incidence of diphtheria and pertussis exemplify the shift in epidemiology to older children/adolescents. Seroprevalence data suggest that immunity to pertussis and diphtheria is below the level of herd immunity in several Asian countries in this population. CONCLUSION: The true burden of diphtheria, pertussis, and tetanus in children aged 3-18 years in Asia is unknown because of weak or absent nationwide surveillance systems. The available evidence highlights the inadequacies in immunity, either by gaps in a recommendation or suboptimal booster coverage, supporting the public health need for booster vaccinations in this population.

Duration of protection against Bordetella pertussis infection elicited by whole-cell and acellular vaccine priming in Polish children and adolescents.

BACKGROUND: In the context of reported resurgence of pertussis in the last decade, researchers hypothesized that acellular (aP) pertussis vaccines elicit a shorter-lived protection compared to whole-cell (wP) pertussis vaccines. However, in the studies seeking to demonstrate this hypothesis, exposure to each vaccine type was not concurrent, and contradictory epidemiologic modeling questioned its validity. The context of pertussis vaccination history in Poland, with both vaccine types used concurrently in comparable proportions, provided an opportunity to investigate this hypothesis. We sought to compare waning of protection by primary series vaccine type by measuring anti-pertussis toxin antibody concentrations as proxy for recent infection. MATERIALS AND METHODS: Serological samples from 2,745 children and adolescents aged ≥5 years and <16 years and with completed 5-dose pertussis vaccination series were tested by ELISA for pertussis toxin (PT) antibodies. Participants were stratified by type of priming vaccine (wP or aP). Vaccination timeliness and priming-specific trends in anti-PT antibody levels by time since last vaccine dose were analyzed. RESULTS: A total of 1,161 (42.5%) children received wP vaccines, and 1,314 (48.1%) received aP vaccines for their primary series and toddler booster. Overall, 53.57% of the subjects received doses 2-4 in a timely manner, while only 41.52% received all 5 doses at the recommended intervals. Using GMCs or seropositivity measures, both priming groups showed a re-increase in anti-PT antibody levels signing infection in recent years from 8 years after the school-entry booster onward. Comparisons did not show any significant differences between the two groups in the timing or intensity of this re-increase. CONCLUSION: Our results clearly confirm that vaccine-elicited immunity against pertussis wanes among adolescents even after a complete infant, toddler and school-entry vaccination series. The timing and intensity of the waning of protection appear similar with whole-cell as with acellular pertussis vaccines.

Impact of COVID-19 on routine immunisation in South-East Asia and Western Pacific: Disruptions and solutions.

BACKGROUND: Data on COVID-19-induced disruption to routine vaccinations in the South-East Asia and Western Pacific regions (SEAR/WPR) have been sparse. This study aimed to quantify the impact of COVID-19 on routine vaccinations by country, antigen, and sector (public or private), up to 1 June 2020, and to identify the reasons for disruption and possible solutions. METHODS: Sanofi Pasteur teams from 19 countries in SEAR/WPR completed a structured questionnaire reporting on COVID-19 disruptions for 13-19 routinely delivered antigens per country, based on sales data, government reports, and regular physician interactions. Data were analysed descriptively, disruption causes ranked, and solutions evaluated using a modified public health best practices framework. FINDINGS: 95% (18/19) of countries reported vaccination disruption. When stratified by country, a median of 91% (interquartile range 77-94) of antigens were impacted. Infancy and school-entry age vaccinations were most impacted. Both public and private sector healthcare providers experienced disruptions. Vaccination rates had not recovered for 39% of impacted antigens by 1 June 2020. Fear of infection, movement/travel restrictions, and limited healthcare access were the highest-ranked reasons for disruption. Highest-scoring solutions were separating vaccination groups from unwell patients, non-traditional vaccination venues, virtual engagement, and social media campaigns. Many of these solutions were under-utilised. INTERPRETATION: COVID-19-induced disruption of routine vaccination was more widespread than previously reported. Adaptable solutions were identified which could be implemented in SEAR/WPR and elsewhere. Governments and private providers need to act urgently to improve coverage rates and plan for future waves of the pandemic, to avoid a resurgence of vaccine-preventable diseases. FUNDING: Sanofi Pasteur.

Vaccine-Related Errors in Reconstitution in South Korea: A National Physicians' and Nurses' Survey.

Vaccine-related errors (VREs) result from mistakes in vaccine preparation, handling, storage, or administration. We aimed to assess physicians' and nurses' experiences of VREs in South Korea, focusing on reconstitution issues, and to understand the barriers to and facilitators of preventing them. This was a cross-sectional study using an internet-based survey to examine experiences of reconstitution-related errors, and experience or preference with regard to ready-to-use vaccines (RTU) by physicians and nurses. A total of 700 participants, including 250 physicians and 450 nurses, responded to the questionnaire. In total, 76.4% and 41.5% of the physicians and nurses, respectively, reported an error related to reconstituted vaccines. All errors had been reported as experienced by between 4.9% and 52.0% of physicians or nurses. The errors were reported to occur in more than one in 100 vaccinations for inadequate shaking of vaccines by 28.0% of physicians and 6.9% of nurses, incomplete aspiration of reconstitution vials by 28.0% of physicians and 6.4% of nurses, and spillage or leakage during reconstitution by 20.8% of physicians and 6.9% of nurses. A total of 94.8% of physicians had experience with RTU vaccines, and all preferred RTU formulations. In conclusion, this study highlights the high frequency and types of reconstitution-related errors in South Korea. RTU vaccines could help reduce the time needed for preparation and reduce the risk of errors in South Korea.

Evaluación genómica en ganado Holstein Colombiano, usando genotipos imputados a densidad media / Genomic Evaluation of Colombian Holstein Cattle Using Imputed Genotypes at Medium Density

RESUMEN Objetivo. El objetivo de este estudio fue determinar la precisión y el sesgo de predicción de valores genómicos directos (VGD) usando genotipos imputados a densidad media, en características productivas y reproductivas en ganado Holstein de Antioquia, Colombia. Materiales y métodos. Fueron genotipificados 31 animales con el chip Illumina BovineLD, 64 con el chip Illumina BovineSNP50v2 y 48 con el chip Illumina BovineHD. La imputación se realizó usando dos paneles de SNPs (6K y 40K) a una densidad 44K, usando el programa FINDHAP.f90 v4. Los efectos de los SNPs fueron estimados mediante el método bayes C, usando genotipos de baja densidad (6K) y genotipos imputados a una densidad media (44_imputado). La precisión y el sesgo de los VGDs fueron determinados mediante validación cruzada. Las características evaluadas fueron: producción de leche (PL), porcentaje de proteína (PRO), porcentaje de grasa (GRA), puntaje de células somáticas (SCS), intervalo entre partos (IEP) y días abiertos (DA). Resultados. Las precisiones de VGD (rpVGD.EBV) en todas las características evaluadas oscilaron entre 0.19 y 0.24 y el sesgo (bVGD.EBV) entre 0.03 y 0.16 cuando se usó el panel 6K y usando el panel 44K_imputado las precisiones fueron mayores, oscilado entre 0.24 y 0.33 y sesgo entre 0.03 y 0.26. Conclusiones. La precisión de predicción de los VGDs fue mayor cuando se usaron genotipos imputados a densidad media, en comparación con la precisión de predicción obtenida empleando genotipos de baja densidad. Por lo cual, en este estudio se concluye que la imputación de genotipos es muy útil dado que aumenta la confiabilidad de la evaluación genómica.

ABSTRACT Objective. The goal of this study was to determine the accuracy and bias of direct genomic values (DGV) using imputed genotypes at medium density in yield- and reproduction-related traits for Holstein cattle from Antioquia, Colombia. Materials and Methods. A total of 31 animals were genotyped with the Illumina BovineLD chip, 64 with Illumina BovineSNP50v2 and 48 with Illumina BovineHD. Two SNP panels (6K and 40K) were imputed to a density of 44K using the FINDHAP.f90 v4 program. The effects of the SNPs were estimated using the Bayes C method, using low-density (6K) genotypes as well as medium-density imputed genotypes (44_imputed). The accuracy and bias of the DGVs were determined by cross-validation. The evaluated traits were: milk yield (MY), percentage of protein (PP), percentage of fat (PF), somatic cell score (SCS), calving interval (CI) and open days (OD). Results. When using the 6K panel, the accuracy values for DGV (rpDGV.EBV) in all the studied traits ranged from 0.19 to 0.24, and the bias (bDGV.EBV) from 0.03 to 0.16. In contrast, using the 44K_imputed panel generated higher accuracy values ranging from 0.24 to 0.33 and a bias ranging from 0.03 to 0.26. Conclusions. The accuracy of prediction the DGV was higher with genotypes imputed to medium densities when compared to the accuracy of prediction obtained using low-density genotypes. Therefore, in this study it is concluded that the imputation of genotypes is very useful, because it improves the reliability of the genomic evaluation.

Altering the motility of Trypanosoma cruzi with rabbit polyclonal anti-peptide antibodies reduces infection to susceptible mammalian cells.

Trypanosoma cruzi's trypomastigotes are highly active and their incessant motility seems to be important for mammalian host cell infection. The kinetoplastid membrane protein-11 (KMP-11) is a protein expressed in all parasite stages, which induces a cellular and humoral immune response in the infected host, and is hypothesized to participate in the parasite's motility. An N-terminal peptide from KMP-11, termed K1 or TcTLE, induced polyclonal antibodies that inhibit parasitic invasion of Vero cells. The goal of this study was to evaluate the motility and infectivity of T. cruzi when exposed to polyclonal anti-TcTLE antibodies. Rabbits were immunized with TcTLE peptide along with FIS peptide as an immunomodulator. ELISA assay results showed that post-immunization sera contained high titers of polyclonal anti-TcTLE antibodies, which were also reactive against the native KMP-11 protein and live parasites as detected by immunofluorescence and flow cytometry assays. Trypomastigotes of T. cruzi were incubated with pre- or post-immunization sera, and infectivity to human astrocytes was assessed by Giemsa staining/light microscope and flow cytometry using carboxyfluorescein diacetate succinimidyl ester (CFSE) labeled parasites. T. cruzi infection in astrocytes decreased approximately by 30% upon incubation with post-immunization sera compared with pre-immunization sera. Furthermore, trypomastigotes were recorded by video microscopy and the parasite's flagellar speed was calculated by tracking the flagella. Trypomastigotes exposed to post-immunization sera had qualitative alterations in motility and significantly slower flagella (45.5 µm/s), compared with those exposed to pre-immunization sera (69.2 µm/s). In summary, polyclonal anti-TcTLE serum significantly reduced the parasite's flagellar speed and cell infectivity. These findings support that KMP-11 could be important for parasite motility, and that by targeting its N-terminal peptide infectivity can be reduced.

Genomic evaluation of Holstein cattle in Antioquia (Colombia): a case study / Evaluación genómica de ganado Holstein en Antioquia (Colombia): estudio de caso / Avaliação genômica do gado Holandês de Antioquia (Colômbia): estudo de caso

Background: DNA markers have been widely used in genetic evaluation throughout the last decade due to the increased reliability of breeding values (BV) they allow, mainly in young animals. Objective: to compare breeding values estimated through the conventional method (best linear unbiased predictor, BLUP) with methods that include molecular markers for milk traits in Holstein cattle in Antioquia (Colombia). Methods: predictions of breeding values were performed using three methods: BLUP, molecular best linear unbiased predictor (MBLUP), and Bayes C. The breeding values were compared using Spearman's correlation coefficient and linear regression coefficient. Results: all Spearman correlation coefficients between breeding values obtained by different methods were greater than 0.5, while linear regression coefficients ranged between -2.10 and 1.58. Conclusions: prediction of breeding values through BLUP, MBLUP and Bayes C showed different results in terms of magnitude from the estimated values. However, animal ranking according to breeding values was not significantly different.

Antecedentes: en la última década, los marcadores de DNA han sido ampliamente usados en evaluaciones genéticas porque incrementan la confiabilidad de valores genéticos principalmente en animales jóvenes. Objetivo: comparar valores genéticos (BV) estimados por el método convencional (mejor estimador lineal insesgado, BLUP) y métodos que incluyen marcadores moleculares para algunas características lecheras en ganado Holstein de Antioquia (Colombia). Métodos: la predicción de valores genéticos se realizó mediante tres métodos: BLUP, mejor predictor lineal insesgado molecular (MBLUP) y Bayes C. Los valores genéticos fueron comparados usando el coeficiente de correlación de Spearman y el coeficiente de regresión lineal. Resultados: todos los coeficientes de correlación de Spearman entre los valores genéticos obtenidos por los diferentes métodos fueron mayores de 0,5. Mientras que los coeficientes de regresión lineal oscilaron entre -2,10 y 1,96. Conclusiones: la predicción de valores genéticos empleando los métodos BLUP, MBLUP y Bayes C fue diferente en términos de la magnitud de los valores estimados. Sin embargo el ranking o clasificación de los animales por sus valores genéticos no fue alterado significativamente.

Antecedentes: na última década, os marcadores moleculares que identificam polimorfismos no DNA têm sido utilizados amplamente nas avaliações genéticas porque aumentam a fiabilidade dos valores genéticos (BV) estimados principalmente em animais jovens. Objetivo: comparar valores genéticos estimados pelo método convencional (melhor preditor linear não-viesado, BLUP) e métodos que incluem marcadores moleculares para algumas características leiteiras no gado holandês de Antioquia (Colômbia). Métodos: as predições dos valores genéticos foram realizadas por meio de três métodos: BLUP, melhor preditor linear não-viesado molecular (MBLUP) e Bayes C. Os valores genéticos foram comparados por meio de coeficientes de correlação de Spearman e de coeficientes de regressão linear. Resultados: os coeficientes de correlação de Spearman entre os valores genéticos obtidos pelos diferentes métodos foram maiores que 0,5. Enquanto os coeficientes de regressão linear variaram entre -2,10 e 1,96. Conclusões: a predição dos valores genéticos usando os métodos BLUP, MBLUP e Bayes C foi diferente em quanto à magnitude dos valores estimados. No entanto, o ranking ou classificação de animais por seus valores genéticos não foi alterada significativamente.

Alleles of the BoLA DRB3.2 gene are associated with mastitis in dairy cows / Alelos del gen BoLA DRB3.2 están asociados con mastitis en vacas lecheras / Alelos BOLA DRB3.2 estão associados à mastite em vacas leiteiras

The Mayor Histocompatibility Complex (MHC) is a pool of genes which regulate both processing and recognition of antigens. The MHC is the main genetic component of the resistance or susceptibility to infectious diseases. In bovines, MHC is known as Bovine Leukocyte Antigen (BoLA), and some of its alleles have been associated with udder health issues. This study evaluated exon-2 polymorphisms of BoLA DRB3 gene in 91 cows of a dairy farm. A total of 66 Holstein and 25 cross breed BON x Holstein (BxH) cows were evaluated. Twenty seven alleles were identified by PCR-RFLP and PCR-SBT. Allelic frequencies varied from 0.8 to 15.9% for the Holstein, and from 2 to 20% for BxH cows. The BoLA DRB3.2*23 was the most frequent allele in both groups. A prospective study was also conducted for cows in production (n=47) during one lactation to determine subclinical mastitis incidence using the California Mastitis Test (CMT). A 38.69% frequency of positive cases was observed. Additionally, a retrospective study was conducted for all the cows (n=91), finding 9.2% incidence of clinical mastitis per year. Possible associations were established using a statistical model to determine the effect of genetic substitution, in which BoLA DRB3.2*24 was used as the substitution allele. Alleles associated with susceptibility to subclinical mastitis were DRB3.2*8 (p<0.10) and DRB3.2*14 (p< 0.01). Allele DRB3.2*33 was associated with resistance to subclinical mastitis (p<0.01). No significant associations were found for clinical mastitis.

El complejo mayor de histocompatibilidad (CMH) es un conglomerado de genes que regulan el procesamiento y reconocimiento de antígenos extraños, siendo el principal componente genético de resistencia o susceptibilidad a enfermedades infecciosas. En bovinos el CMH es conocido como antígeno leucocitario bovino (BoLA) y algunos alelos de este han sido asociados con problemas de salud de la ubre. En este estudio se evaluaron polimorfismos del exón 2 del gen BoLA DRB3 en 91 animales, 66 vacas de raza Holstein y 25 vacas del cruce de razas BON x Holstein (BxH) del Hato Paysandú de la Universidad Nacional de Colombia. Fueron identificados 27 alelos mediante PCR-RFLP y confirmados por PCR-SBT, encontrando frecuencias alélicas desde 0.8 hasta 15.9% en la raza Holstein y desde 2 hasta 20% en BxH. El alelo más frecuente en los dos grupos fue el alelo BoLA DRB3.2*23. Para determinar la frecuencia de mastitis subclínica, se realizó un estudio prospectivo con animales en producción (n = 47) durante un periodo de una lactancia, empleando la prueba CMT (California Mastitis Test) y se determinó una frecuencia de 38.69% de casos positivos (reacciones positivas: una, dos y tres cruces) en promedio. Para mastitis clínica se realizó un estudio retrospectivo en toda la población (n=91), a partir de los registros clínicos y se determinó una incidencia anual de 9.2%. Adicionalmente se establecieron asociaciones potenciales utilizando un modelo estadístico para determinar el efecto de sustitución genética en el cual se empleó el alelo BoLA DRB3.2*24 como alelo de sustitución. Los alelos asociados con susceptibilidad a mastitis subclínica fueron DRB3.2*8 (p<0.10) y el *14 (p< 0.01), de otro lado el alelo *33 fue asociado con resistencia a esta misma enfermedad (p< 0.01). Para mastitis clínica no se encontraron asociaciones significativas.

O complexo principal de histocompatibilidade (CMH) é um conjunto de genes que regulam o processamento e reconhecimento de antígenos estranhos, o principal componente genético da resistência ou suscetibilidade a doenças infecciosas. Em bovinos, o CMH é conhecida como antígeno leucocitário bovino (BoLA) e alguns alelos têm sido associados a problemas de saúde do úbere. Neste estudo, os polimorfismos do éxon 2 do gene BoLA DRB3 em 91 animais, 66 vacas e 25 vacas da raça Holandesa no cruzamento BON x Holandês (BXH) do rebanho Paysandú, da Universidade Nacional da Colômbia. Foram identificados 27 alelos foram identificados por PCR-RFLP e confirmados por PCR-SBT, encontrando frequências alélicas de 0.8 - 15.9% para a raça Holandesa e 2 - 20% em BXH. O alelo mais frequente nos dois grupos foi BoLA DRB3.2*23. Para determinar a frequência de mastite subclínica, um estudo prospectivo foi realizado com animais de produção (n=47) durante o período de lactação, utilizando o CMT (Califórnia Mastite Teste) e foi determinada uma frequência de 38,69% de casos positivos (reacções positivas: uma, duas e três cruzes) em média. Para a mastite clínica foi feito um estudo retrospectivo em toda a população (n=91), a partir de casos clínicos e foi encontrada uma incidência anual de 9.2%. Além disso, foram estabelecidas potenciais associações, utilizando um modelo estatístico para determinar o efeito da substituição genética do alelo DRB3.2*24. Os alelos associados à susceptibilidade à mastite foram DRB3.2 * 8 (p<0.10) e o * 14 (p<0.01), o alelo * 33 esteve associado com a resistência à mesma doença (p<0.01). Para a mastite clínica não foram encontradas associações significativas.

Toll-like receptor-4 genotype influences the survival of cystic fibrosis mice.

Toll-like receptor (Tlr) 4 is a lipopolysaccharide (LPS) receptor that contributes to the regulation of intestinal cell homeostasis, a condition that is altered in the intestines of cystic fibrosis mice. Herein, we assessed whether Tlr4 genotype influences cystic fibrosis intestinal disease by producing and phenotyping 12-wk (adult)- and 4-day (neonate)-old mice derived from BALB cystic fibrosis transmembrane conductance regulator, Cftr(+/tm1Unc) and C.C3-Tlr4(Lps-d)/J (Tlr4(-/-)), progenitors. Intestinal disease was assayed through mouse survival, crypt-villus axis (CVA) length, cell proliferation, bacterial load, bacterial classification, inflammatory cell infiltrate, and mucus content measures. Of the 77 Cftr(-/-) (CF) mice produced, only one Cftr/Tlr4 double-mutant mouse lived to the age of 12 wk while the majority of the remainder succumbed at approximately 4 days of age. The survival of CF Tlr4(+/-) mice exceeded that of both CF Tlr4(+/+) and Cftr/Tlr4 double-mutant mice. Adult CF mice presented increased Tlr4 expression, CVA length, crypt cell proliferation, and bacterial load relative to non-CF mice, but no differences were detected in Tlr4(+/-) compared with Tlr4(+/+) CF mice. The double-mutant neonates did not differ from Tlr4(+/+) or Tlr4(+/-) CF mice by intestinal CVA length or bacterial load, but fewer Tlr4(+/-) CF neonates presented with luminal mucus obstruction in the distal ileum, and the intestinal mast cell increase of CF mice was not evident in double-mutant neonates. We conclude that Tlr4 deficiency reduces the survival, but does not alter the intestinal phenotypes, of extended CVA or increased bacterial load in BALB CF mice.

Intestinal phenotype of variable-weight cystic fibrosis knockout mice.

Cystic fibrosis (CF) transmembrane conductance regulator (Cftr) knockout mice present the clinical features of low body weight and intestinal disease permitting an assessment of the interrelatedness of these phenotypes in a controlled environment. To identify intestinal alterations that are affected by body weight in CF mice, the histological phenotypes of crypt-villus axis height, goblet cell hyperplasia, mast cell infiltrate, crypt cell proliferation, and apoptosis were measured in a population of 12-wk-old (C57BL/6 x BALB/cJ) F2 Cftr(tm1UNC) and non-CF mice presenting a range of body weight. In addition, cardiac blood samples were assessed, and gene expression profiling of the ileum was completed. Crypt-villus axis height decreased with increasing body weight in CF but not control mice. Intestinal crypts from CF mice had fewer apoptotic cells, per unit length, than did non-CF mice, and normalized cell proliferation was similar to control levels. Goblet cell hyperplasia and mast cell infiltration were increased in the CF intestine and identified to be independent of body weight. Blood triglyceride levels were found to be significantly lower in CF mice than in control mice but were not dependent on CF mouse weight. By expression profiling, genes of DNA replication and lipid metabolism were among those altered in CF mice relative to non-CF controls, and no differences in gene expression were measured between samples from CF mice in the 25th and 75th percentile for weight. In this CF mouse model, crypt elongation, due to an expanded proliferative zone and decreased apoptosis, was identified to be dependent on body weight.

Experimental rhinovirus challenges in adults with mild asthma: response to infection in relation to IgE.

BACKGROUND: Although most children and young adults with asthma are atopic, exacerbations of asthma are frequently associated with viral respiratory tract infections, especially those caused by rhinovirus (HRV). OBJECTIVE: Young atopic adults with mild asthma were evaluated before and during an experimental HRV infection to test the hypothesis that airway inflammation before virus inoculation may be a risk factor for an adverse response to HRV. METHODS: Experimental HRV infections were evaluated in 16 allergic volunteers with mild asthma and 9 nonatopic control patients (age, 18 to 30 years). Before virus inoculation, each participant was screened with tests for lung function, prick skin tests for sensitization to common aeroallergens, measurements of total serum IgE, and serum neutralizing antibody to rhinovirus-16 (the serotype used for inoculation). The response to infection was monitored for 21 days by using symptom diary cards, tests for lung function, and markers of airway inflammation in nasal washes, blood, and expired air. RESULTS: During the infection, asthmatic patients had cumulative upper and lower respiratory tract symptom scores that were significantly greater over the course of 21 days than scores from the control patients. At baseline, the asthmatic patients also had increased sensitivity to methacholine and significantly lower values for FEV(1) (percent predicted) than the control patients (geometric mean and intraquartile values: 87% [79% to 91%] for the asthmatic patients and 101% [90% to 104%] for the control patients, P <.03). Among the patients with mild asthma, 6 had levels of total serum IgE that were substantially elevated (range, 371 to 820 IU/mL) compared with 10 who had lower levels (range, 29 to 124 IU/mL). Those with high levels of IgE had significantly greater lower respiratory tract symptom scores during the initial 4 days of the infection than the low IgE group. They also had higher total blood eosinophil counts at baseline, increased eosinophil cationic protein in their nasal washes (>200 ng/mL), and augmented levels of expired nitric oxide at baseline and during peak cold symptoms. In contrast, levels of soluble intracellular adhesion molecule-1 in nasal wash supernatants from the asthmatic patients with high IgE were diminished, both at baseline and during the infection. CONCLUSIONS: The reduced lung function and increased markers of inflammation observed before virus inoculation in the asthmatic patients who had high levels of total serum IgE may be risk factors for an adverse response to infections with HRV.