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BACKGROUND: Concerns remain about lower effectiveness and waning immunity of rotavirus vaccines in resource-poor populations. We assessed vaccine effectiveness against rotavirus in Guatemala, where both the monovalent (RV1; 2-dose series) and pentavalent (RV5; 3-dose series) vaccines were introduced in 2010. METHODS: A case-control evaluation was conducted in 4 hospitals from January 2012 to August 2013. Vaccine status was compared between case patients (children with laboratory-confirmed rotavirus diarrhea) and 2 sets of controls: nondiarrhea "hospital" controls (matched by birth date and site) and nonrotavirus "test-negative" diarrhea controls (adjusted for age, birth month/year, and site). Vaccine effectiveness ([1 - odds ratio of vaccination] × 100%) was computed using logistic regression models. RESULTS: We evaluated 213 case patients, 657 hospital controls, and 334 test-negative controls. Effectiveness of 2-3 doses of a rotavirus vaccine against rotavirus requiring emergency department visit or hospitalization was 74% (95% confidence interval [CI], 58%-84%) with hospital controls, and 52% (95% CI, 26%-69%) with test-negative controls. Using hospital controls, no significant difference in effectiveness was observed between infants 6-11 months (74% [95% CI, 18%-92%]) and children ≥12 months of age (71% [95% CI, 44%-85%]) (P= .85), nor between complete courses of RV1 (63% [95% CI, 23%-82%]) and RV5 (69% [95% CI, 29%-87%]) (P= .96). An uncommon G12P[8] strain, partially heterotypic to strains in both vaccines, was identified in 89% of cases. CONCLUSIONS: RV1 and RV5 were similarly effective against severe rotavirus diarrhea caused by a heterotypic strain in Guatemala. This supports broader implementation of rotavirus vaccination in low-income countries where >90% global deaths from rotavirus occur.
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Infecciones por Rotavirus/prevención & control , Vacunas contra Rotavirus/inmunología , Estudios de Casos y Controles , Preescolar , Diarrea/epidemiología , Diarrea/virología , Servicio de Urgencia en Hospital , Femenino , Guatemala/epidemiología , Hospitalización , Humanos , Lactante , Modelos Logísticos , Masculino , Oportunidad Relativa , Pobreza , Rotavirus/inmunología , Rotavirus/aislamiento & purificación , Infecciones por Rotavirus/diagnóstico , Infecciones por Rotavirus/epidemiología , Infecciones por Rotavirus/virología , Vacunas contra Rotavirus/administración & dosificación , Vacunación , Potencia de la Vacuna , Vacunas Atenuadas/administración & dosificación , Vacunas Atenuadas/inmunologíaRESUMEN
Introduction: Clarithromycin is the first-line antibiotic for the treatment of Helicobacter pylori infection. Bacterial resistance is mainly due to the presence of specific mutations in the 23S ribosomal RNA (rRNA) gene. Objective: To determine the frequency of A2143G and A2142G specific mutations in the 23S rRNA gene associated with clarithromycin resistance of H. pylori in samples from patients with dyspeptic manifestations in Medellín, northwestern Colombia. Materials and methods: DNA was extracted from gastric biopsy samples of patients with dyspeptic manifestations seen at an endoscopy unit in Medellín between 2016 and 2017. PCR was performed to amplify the bacterial s and m vacA regions, and a region in the 23S rRNA gene. The presence of the A2142G and A2143G mutations was determined using the restriction fragment length polymorphism (RFLP) technique with the BbsI and BsaI enzymes, respectively. Results: The prevalence of infection was 44.2% (175/396), according to the histopathology report. The positive samples were analyzed and the three regions of the bacterial genome were amplified in 143 of the 175 samples. The A2143G and A2142G mutations were identified in 27 samples (18.8%, 27/143). The most frequent mutation was A2143G (81.5%, 22/27). Conclusions: We found a high prevalence of H. pylori mutations associated with clarithromycin resistance in the study population. Further studies are required to determine the bacterial resistance in the Colombian population in order to define first line and rescue treatments.
Introducción. La claritromicina es el antibiótico de primera línea para el tratamiento de la infección por Helicobacter pylori. La resistencia bacteriana se produce principalmente por mutaciones puntuales del gen ARN ribosómico 23S (ARNr 23S). Objetivo. Determinar la frecuencia de las mutaciones puntuales A2143G y A2142G del gen ARNr 23S asociadas con la resistencia de H. pylori a la claritromicina en muestras de pacientes con manifestaciones dispépticas en Medellín, región noroccidental de Colombia. Materiales y métodos. Se extrajo ADN a partir de muestras de biopsia gástrica obtenidas de pacientes con manifestaciones dispépticas atendidos en una unidad de endoscopia entre el 2016 y el 2017. Mediante reacción en cadena de la polimerasa (PCR), se amplificaron las regiones s y m del gen vacA y una región del gen ARNr 23S bacteriano. La presencia de las mutaciones A2142G y A2143G se determinó por la técnica de polimorfismos de longitud de fragmentos de restricción (RFLP) con las enzimas BbsI y BsaI, respectivamente. Resultados. Se encontró una prevalencia de infección de 44,2 % (175/396), según el informe de histopatología. En 143 de estas 175 muestras positivas se amplificaron las tres regiones del genoma bacteriano. Se identificaron las mutaciones A2143G y A2142G en 27 muestras (18,8 %; 27/143), la mutación más frecuente fue la A2143G (81,5 %; 22/27). Conclusiones. Hubo una gran prevalencia de mutaciones asociadas con la resistencia de H. pylori a la claritromicina en la población de estudio. Se requieren estudios adicionales para establecer la resistencia bacteriana en la población colombiana y, así, determinar los tratamientos de primera línea y de rescate.
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Antibacterianos/farmacología , Claritromicina/farmacología , Farmacorresistencia Bacteriana/genética , Genes Bacterianos , Genes de ARNr , Infecciones por Helicobacter/microbiología , Helicobacter pylori/genética , Mutación Missense , Mutación Puntual , ARN Bacteriano/genética , ARN Ribosómico 23S/genética , Adulto , Anciano , Colombia/epidemiología , Estudios Transversales , Dispepsia/epidemiología , Dispepsia/microbiología , Femenino , Gastritis/epidemiología , Gastritis/microbiología , Infecciones por Helicobacter/epidemiología , Helicobacter pylori/efectos de los fármacos , Helicobacter pylori/aislamiento & purificación , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Adulto JovenRESUMEN
Multiplex polymerase chain reaction (PCR) platforms have enhanced understanding of intestinal pathogens in low- and middle-income countries (LMICs). However, few such studies have been performed in Latin America, where poverty, poor sanitation, and undernutrition persist. Multiplex PCR (BioFire, Salt Lake City, UT) was used to identify viral, bacterial, and parasitic pathogens in stool collected on day 1 and 31 from children aged 6 to 35 months with acute, non-bloody diarrhea in two locations (rural and urban) in Guatemala. We analyzed correlation between pathogens and clinical, demographic, and socioeconomic variables; described patterns of pathogen acquisition, persistence, and clearance over the 30-day period; and calculated population attributable fractions (PAFs) for diarrheal causation for individual pathogens. We analyzed 316 subjects (144 urban; 172 rural) enrolled between March 2015 and January 2016. Rural subjects had significantly more malnutrition, animal exposure, and unimproved water/sanitation infrastructure. The majority of subjects had multiple pathogens/sample (4.8 rural and 2.7 urban). Few meaningful correlates were identified between individual pathogens and clinical, demographic, or environmental variables. Escherichia coli pathotypes, Shigella, Campylobacter, and Giardia had high rates of persistence between initial and 30-day follow-up. Statistically significant adjusted PAFs were identified for Campylobacter (14.9%, 95% CI: 3.2-23.1), norovirus (10.2%, 95% CI: 0.4-17.1), sapovirus (7.6%, 95% CI: 2.3-10.9), and adenovirus 40/41 (5.6%, 95% CI: 0.3-8.7). These observations further characterize the diversity and complexity of enteric pathogens in children in LMICs. Patterns of chronic symptomatic and asymptomatic infection among Latin American children are similar to those observed in other LMIC regions. Findings have direct implications for practitioners treating individuals with acute infectious diarrhea and should inform regional public health strategies.
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Diarrea/diagnóstico , Reacción en Cadena de la Polimerasa Multiplex , Población Rural , Población Urbana , Enfermedad Aguda , Animales , Bacterias/genética , Bacterias/patogenicidad , Preescolar , Coinfección/diagnóstico , Coinfección/microbiología , Coinfección/parasitología , Coinfección/virología , Diarrea/microbiología , Diarrea/parasitología , Diarrea/virología , Femenino , Tracto Gastrointestinal/microbiología , Tracto Gastrointestinal/parasitología , Tracto Gastrointestinal/virología , Humanos , Lactante , Masculino , Parásitos/genética , Parásitos/patogenicidad , Virus/genética , Virus/patogenicidadRESUMEN
Vaccine hesitancy is a continuum of behaviors ranging from delay in receipt to vaccination refusal. Prior studies have typically focused on high-income countries, where vaccine hesitancy is particularly prevalent in more affluent groups, but the relationship between socioeconomic status and vaccine hesitancy in Low- and Middle-Income Countries (LMICs) is less clear. The aim of this study was to describe vaccine hesitancy in five LMICs. Mothers of children in Sirajganj, Bangladesh (n = 60), Shanghai, China (n = 788), Addis Ababa, Ethiopia (n = 341), Guatemala City and Quetzaltenango, Guatemala (n = 767), and Chandigarh, India (n = 309), completed a survey between 2016 and 2018 using the WHO's 10-item Vaccine Hesitancy Scale. The scores of different constructs were compared across countries and by the mother's education level using linear regression models with generalized estimating equations. Compared to mothers in China, mothers in Bangladesh perceived less vaccination benefit (ß: 0.56, P = 0.0001), however, mothers in Ethiopia (ß: -0.54, P < 0.0001) and Guatemala (ß: -0.74, P = 0.0004) perceived greater benefit. Education level was not significantly linked with vaccine hesitancy. Local circumstances are important to consider when developing programs to promote vaccines. We did not find consistent associations between education and vaccine hesitancy. More research is needed to understand socio-cultural influences on vaccine decision-making.
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OBJECTIVE: Millions of infants worldwide remain under-immunized and at risk for unnecessary morbidity and mortality. Text messaging may offer a low-cost solution. We aimed to evaluate text message reminders to improve infant immunization in Guatemala. METHODS: A randomized clinical trial was conducted at four public health clinics in rural and urban Guatemala. Infants ages six weeks to six months presenting for the first visit of the primary immunization series were randomly and equally allocated to an intervention or usual care group. Intervention participants were sent three text reminders before the second and third vaccine visits. The main outcome was timeliness of the second and third visits of the primary immunization series. RESULTS: Of 1088 families approached for enrollment between March to November 2016, 871 were eligible and 720 (82.7%) participated; only 54 families did not own a cell phone. Due to country-wide vaccine shortages, visit completion was used as a proxy for overall immunization coverage. In intention to treat analysis, both intervention and usual care groups had high rates of visit completion, but intervention participants presented on the scheduled date more often (151 [42.2%] of 358 intervention vs. 111 [30.7%] of 362 usual care participants for visit 2, pâ¯=â¯0.001, and 112 [34.0%] of 329 intervention vs. 90 [27.0%] of 333 usual care participants for visit 3, pâ¯=â¯0.05). Intervention caregivers were significantly more likely to want to receive future text message reminders for vaccines and other appointments and were more willing to pay for these reminders. CONCLUSION: Caregivers who were sent text message reminders in urban and rural Guatemala were less delayed for their child's immunization visits and reported high user satisfaction. Text message reminders may be an effective tool to increase infant vaccination coverage in low-income settings by reminding parents to vaccinate. TRIAL REGISTRATION: NCT02567006 at clinicaltrials.gov.
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Inmunización , Sistemas Recordatorios , Envío de Mensajes de Texto , Adulto , Citas y Horarios , Teléfono Celular , Escolaridad , Femenino , Guatemala , Humanos , Lactante , Masculino , Edad Materna , Población Rural , Población UrbanaRESUMEN
Introduction: One of the most important risk factors for hepatocellular carcinoma (HCC) is alcohol consumption: Studies in different populations suggest that the risk of liver disease could be associated with genetic variants of the enzymes involved in alcohol metabolism, such as alcohol dehydrogenase (ADH) and cytochrome P450 CYP2E1. Objective: To identify and characterize the allelic variants of ADH1B, ADH1C and CYP2E1 genes in Colombian patients with cirrhosis and/or HCC. Materials and methods: We included samples from patients attending the hepatology unit between 2005-2007 and 2014-2016 of a hospital in Medellin. Samples were genotyped using PCR-RFLP. We compared the results with two control groups and the 1000 Genomes Project database. Results: We collected 97 samples from patients with a diagnosis of cirrhosis and/or HCC. The two main risk factors were chronic alcohol consumption (18.6%) and cholangiopathies (17.5%). The most frequent genotypes in the study population were ADH1B*1/1 (82%), ADH1C*1/1 (59%), and CYP2E1*C/C (84%). Conclusions: This first study of polymorphisms in Colombian patients diagnosed with cirrhosis and/or HCC showed genotypes ADH1B*1/1, ADH1C*1/1 and CYP2E1*C/C as the most frequent. We found no significant differences in the genotype frequency between cases and controls. Further studies are necessary to explore the association between polymorphisms and the risk of end-stage liver disease from alcohol consumption.
Introducción. Uno de los principales factores de riesgo del carcinoma hepatocelular es el consumo crónico de alcohol. En estudios en diferentes poblaciones, se sugiere que las variantes genéticas de las enzimas que participan en el metabolismo del alcohol, como la alcohol deshidrogenasa (ADH) y la citocromo P450 (CYP2E1), estarían asociadas con riesgo de enfermedades hepáticas terminales.Objetivo. Identificar y caracterizar las variantes alélicas de los genes ADH1B, ADH1C y CYP2E1 en pacientes colombianos con diagnóstico de cirrosis y carcinoma hepatocelular.Materiales y métodos. Se incluyeron muestras de pacientes atendidos entre el 2005 y el 2007, y entre el 2014 y el 2016, en la unidad de hepatología de un hospital de Medellín. La genotipificación de las muestras se hizo mediante reacción en cadena de la polimerasa (Polymerase Chain Reaction, PCR) con análisis de los polimorfismos en la longitud de los fragmentos de restricción (Restriction Fragment Length Polymorphism, RFLP). Los resultados se compararon con los de dos grupos de control y con lo reportado en la base de datos del 1000 Genomes Project.Resultados. Se recolectaron 97 muestras de pacientes con diagnóstico de cirrosis y carcinoma hepatocelular. Los dos factores de riesgo más frecuentes fueron el consumo crónico de alcohol (18,6 %) y las colangiopatías (17,5 %). Los genotipos más frecuentes en la población de estudio fueron el ADH1B*1/1 (82 %), el ADH1C*1/1 (59 %) y el CYP2E1*C/C (84 %).Conclusiones. En este primer estudio de los polimorfismos en pacientes colombianos con diagnóstico de cirrosis y carcinoma hepatocelular, los genotipos más frecuentes fueron el ADH1B*1/1, el ADH1C*1/1 y el CYP2E1*C/C. No se observaron diferencias estadísticamente significativas en la frecuencia de los genotipos entre los casos y los controles. Se requieren estudios adicionales en población colombiana para evaluar el riesgo de la enfermedad hepática terminal por consumo crónico de alcohol y laasociación con los polimorfismos.
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Alcohol Deshidrogenasa/genética , Carcinoma Hepatocelular/genética , Citocromo P-450 CYP2E1/genética , Cirrosis Hepática/genética , Neoplasias Hepáticas/genética , Polimorfismo Genético , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
BACKGROUND: Despite safe and effective childhood immunizations, decreased acceptance of vaccines has become an emerging global problem. The WHO SAGE Working Group on Vaccine Hesitancy developed a common diagnostic tool, the Vaccine Hesitancy Scale (VHS), to identify and compare hesitancy in different global settings. We field tested the VHS in rural and urban Guatemala. METHODS: We analyzed data from the enrollment visit of a study conducted at four public health clinics in Guatemala. Infants ages 6â¯weeks-6â¯months presenting for their first wellness visit were enrolled March-November 2016. Parents completed a demographic survey that included the 10 dichotomous and 10 Likert scale VHS questions. Chi-square or Fisher's exact for categorical and ANOVA test for continuous variables were used to assess significance levels in survey differences. We conducted a factor analysis to assess the Likert scale questions. RESULTS: Of 1088 families screened, 871 were eligible and 720 (82.7%) participated. No parent had ever refused a vaccination, and only eight parents (1.1%) had been reluctant or hesitated to get a vaccination for their children. However, only 40.8% (nâ¯=â¯294) of parents said that they think most parents like them have their children vaccinated with all the recommended vaccines. Factor analysis identified two underlying constructs that had eigenvalues of 1.0 or greater and a substantive lack of variability in response across the Likert scale. There were consistent differences between how study clinics responded to the ordinal scaling. CONCLUSION: Our results suggest problems with interpretation of the VHS, especially in the presence of vaccine shortages and using a Likert scale that does not resonate across diverse cultural settings. Our factor analysis suggests that the Likert scale items are more one-dimensional and do not represent the multiple constructs of vaccine hesitancy. We suggest more work is needed to refine this survey for improved reliability and validity. Clinical Trial Registry: NCT02567006.
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Vacunas/uso terapéutico , Adolescente , Adulto , Análisis de Varianza , Femenino , Guatemala , Humanos , Masculino , Aceptación de la Atención de Salud , Negativa del Paciente al Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Despite efforts to promote vaccination in low- and middle-income countries (LMICs), over 20 million infants remain under-immunized and at risk for unnecessary morbidity and mortality. Mobile health technologies, such as Short Message Service (SMS) texts, have tremendous and untapped potential for disease management. Patient reminder systems are an important mechanism for improving childhood vaccination coverage and can be easily adapted to SMS platforms. However, current research lacks an understanding of the barriers and facilitators to mHealth program design, implementation, and scale in LMICs. METHODS: We analyzed survey data collected March-November 2016 at the enrollment visit from a randomized controlled trial conducted at public health clinics in urban and rural Guatemala. Participants included eligible infants 6 weeks to 6 months of age receiving the first dose of the primary immunization series. At least one parent needed to own a mobile phone and be capable of deciphering SMS. Chi-square or Fisher's exact and Student's t-test were used to assess significance levels in demographic differences to describe factors that contribute to the feasibility of using an SMS-based vaccination reminder system. RESULTS: Of 1,088 families approached for enrollment, 871 were eligible and 720 (82.7%) participated with equal numbers of urban and rural children enrolled; 54 parents did not own a mobile phone with SMS capability and three parents could not use SMS. There was no significant difference between urban and rural maternal mobile phone ownership (94.4% vs. 93.3%, P=0.53), but more urban fathers owned mobile phones (72.8% vs. 47.1%, P<0.0001) and, overall, more mothers compared to fathers owned mobile phones (93.9% vs. 61.1%, P<0.0001). Most families (90.4%) chose to have reminders sent to the mother. Urban participants reported more mobile phones present in the home (P<0.0001), but rural participants reported more telephone landlines (34.7% vs. 15.6%, P<0.0001). Most participants reported a daily average of ≤5 telephone calls made (87.4%), ≤10 texts sent (91.0%), and ≤10 texts received (89.9%), with urban families reporting greater telephone usage (P=0.006, P<0.001, and P<0.001 respectively). Parents preferred to make calls over sending texts (74.7% vs. 25.3%, P<0.0001), with more urban families preferring text messaging (31.9% vs. 18.6%, P<0.0001). CONCLUSIONS: Our study results provide important insight into mobile phone access, usage, and preferences for voice and text communication across rural and urban populations of an LMIC that can be used to inform future mHealth interventions. Our findings suggest that offering a combination of more traditional communication methods with newer, modern technologies may be more effective at reminding families about vaccination visits, particularly for our rural population, and that targeting mothers for mobile phone interventions may provide the greatest benefits. Overall, our study suggests that using SMS reminders in LMICs can be a feasible tool for public health interventions.
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BACKGROUND: Treatments for paediatric diarrhoeal disease are limited. We assessed the impact of a bovine colostrum and egg-based treatment designed to reduce diarrhoea duration through non-specific and pathogen-directed mechanisms in children. METHODS: Randomised, double-blind, placebo-controlled trial of PTM202, derived from bovine colostrum and hyperimmune hen's egg on the duration of acute diarrhoeal disease in Guatemalan children. PTM202 contains specific immunoglobulins that target rotavirus, enterotoxigenic Escherichia coli, Shiga toxin-producing E. coli and Salmonella. Children aged 6-35 months presenting to three sites (one rural and two urban) with acute non-bloody diarrhoea were computer randomised to receive three daily doses of PTM202 or placebo. The primary outcome was the post-treatment duration of diarrhoea assessed in the per protocol population. Diarrhoeal pathogens were identified in stool by multiplex PCR (FilmArray Gastrointestinal-Panel, BioFire, Salt Lake City, Utah, USA). Key secondary outcomes included postdiarrhoeal weight gain and impact on diarrhoeal duration stratified by study site and presence of PTM202-targeted organisms in stool at enrolment. Safety was assessed in all participants. RESULTS: From 9 March 2015 to 25 January 2016, 325 children were enrolled, and 301 (154 intervention and 147 placebo) were analysed for the primary outcome. No difference in diarrhoea duration was observed between intervention and placebo in the total population, but a significant reduction was observed in the treatment group among children with at least one targeted pathogen in stool (HR=1.46, P=0.02), an effect most pronounced in urban subjects (HR 2.20, P=0.007) who had fewer stool pathogens and better nutritional status. No impact on 2-week or 4-week weight gain was noted. No adverse events attributed to PTM202 occurred. CONCLUSION: Results demonstrate the potential to target specific pathogens occurring in children with acute non-bloody diarrhoea and shorten illness duration using a novel, safe, nutrition-based intervention. PTM202 may represent a new tool to ameliorate the effects of acute diarrhoeal disease in low/middle-income populations. TRIAL REGISTRATION NUMBER: NCT02385773; Results.
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BACKGROUND: Patient reminder systems are an evidence-based way to improve childhood vaccination rates but are difficult to implement in low- and middle-income countries (LMICs). Short Message Service (SMS) texts may offer a potential low-cost solution, especially in LMICs where mobile phones are becoming more ubiquitous. OBJECTIVE: To determine if an SMS-based vaccination reminder system aimed at improving completion of the infant primary immunization series is feasible and acceptable in Guatemala. METHODS: A pilot randomized controlled trial was conducted at two public health clinics in Guatemala City. Infants aged 8-14 weeks presenting for the first dose of the primary immunization series were enrolled in March-April 2013. Participants randomized into the intervention received three SMS reminders one week before the second and third dose. A follow-up acceptability survey was administered to both groups. RESULTS: The participation rate was 86.8% (321/370); 8 did not own a cell phone and 12 could not use SMS. 96.9% of intervention parents were sent at least one SMS reminder prior to visit 2 and 96.3% prior to visit 3. Both intervention and usual care participants had high rates of vaccine and visit completion, with a non-statistically significant higher percentage of children in the intervention completing both visit 2 (95.0% vs. 90.1%, p=.12) and visit 3 (84.4% vs. 80.7%, p=.69). More intervention vs. usual care parents agreed that SMS reminders would be helpful for remembering appointments (p<.0001), agreed to being interested in receiving future SMS reminders (p<.0001), and said that they would be willing to pay for future SMS reminders (p=.01). CONCLUSION: This proof of concept evaluation showed that a new application of SMS technology is feasible to implement in a LMIC with high user satisfaction. Larger studies with modifications in the SMS system are needed to determine effectiveness (Clinical Trial Registry NCT01663636).
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Padres , Sistemas Recordatorios , Envío de Mensajes de Texto , Vacunación , Adulto , Citas y Horarios , Teléfono Celular , Femenino , Guatemala , Humanos , Lactante , Masculino , Encuestas y Cuestionarios , Adulto JovenRESUMEN
Resumen Introducción. La claritromicina es el antibiótico de primera línea para el tratamiento de la infección por Helicobacter pylori. La resistencia bacteriana se produce principalmente por mutaciones puntuales del gen ARN ribosómico 23S (ARNr 23S). Objetivo. Determinar la frecuencia de las mutaciones puntuales A2143G y A2142G del gen ARNr 23S asociadas con la resistencia de H. pylori a la claritromicina en muestras de pacientes con manifestaciones dispépticas en Medellín, región noroccidental de Colombia. Materiales y métodos. Se extrajo ADN a partir de muestras de biopsia gástrica obtenidas de pacientes con manifestaciones dispépticas atendidos en una unidad de endoscopia entre el 2016 y el 2017. Mediante reacción en cadena de la polimerasa (PCR), se amplificaron las regiones s y m del gen vacA y una región del gen ARNr 23S bacteriano. La presencia de las mutaciones A2142G y A2143G se determinó por la técnica de polimorfismos de longitud de fragmentos de restricción (RFLP) con las enzimas BbsI y BsaI, respectivamente. Resultados. Se encontró una prevalencia de infección de 44,2 % (175/396), según el informe de histopatología. En 143 de estas 175 muestras positivas se amplificaron las tres regiones del genoma bacteriano. Se identificaron las mutaciones A2143G y A2142G en 27 muestras (18,8 %; 27/143), la mutación más frecuente fue la A2143G (81,5 %; 22/27). Conclusiones. Hubo una gran prevalencia de mutaciones asociadas con la resistencia de H. pylori a la claritromicina en la población de estudio. Se requieren estudios adicionales para establecer la resistencia bacteriana en la población colombiana y, así, determinar los tratamientos de primera línea y de rescate.
Abstract Introduction: Clarithromycin is the first-line antibiotic for the treatment of Helicobacter pylori infection. Bacterial resistance is mainly due to the presence of specific mutations in the 23S ribosomal RNA (rRNA) gene. Objective: To determine the frequency of A2143G and A2142G specific mutations in the 23S rRNA gene associated with clarithromycin resistance of H. pylori in samples from patients with dyspeptic manifestations in Medellín, northwestern Colombia. Materials and methods: DNA was extracted from gastric biopsy samples of patients with dyspeptic manifestations seen at an endoscopy unit in Medellín between 2016 and 2017. PCR was performed to amplify the bacterial s and m vacA regions, and a region in the 23S rRNA gene. The presence of the A2142G and A2143G mutations was determined using the restriction fragment length polymorphism (RFLP) technique with the BbsI and BsaI enzymes, respectively. Results: The prevalence of infection was 44.2% (175/396), according to the histopathology report. The positive samples were analyzed and the three regions of the bacterial genome were amplified in 143 of the 175 samples. The A2143G and A2142G mutations were identified in 27 samples (18.8%, 27/143). The most frequent mutation was A2143G (81.5%, 22/27). Conclusions: We found a high prevalence of H. pylori mutations associated with clarithromycin resistance in the study population. Further studies are required to determine the bacterial resistance in the Colombian population in order to define first line and rescue treatments.
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Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , ARN Bacteriano/genética , ARN Ribosómico 23S/genética , Helicobacter pylori/genética , Infecciones por Helicobacter/microbiología , Mutación Puntual , Claritromicina/farmacología , Genes de ARNr , Mutación Missense , Farmacorresistencia Bacteriana/genética , Genes Bacterianos , Antibacterianos/farmacología , Prevalencia , Estudios Transversales , Helicobacter pylori/aislamiento & purificación , Helicobacter pylori/efectos de los fármacos , Infecciones por Helicobacter/epidemiología , Colombia/epidemiología , Dispepsia/microbiología , Dispepsia/epidemiología , Gastritis/microbiología , Gastritis/epidemiologíaRESUMEN
Introducción. Uno de los principales factores de riesgo del carcinoma hepatocelular es el consumo crónico de alcohol. En estudios en diferentes poblaciones, se sugiere que las variantes genéticas de las enzimas que participan en el metabolismo del alcohol, como la alcohol deshidrogenasa (ADH) y la citocromo P450 (CYP2E1), estarían asociadas con riesgo de enfermedades hepáticas terminales. Objetivo. Identificar y caracterizar las variantes alélicas de los genes ADH1B, ADH1C y CYP2E1 en pacientes colombianos con diagnóstico de cirrosis y carcinoma hepatocelular. Materiales y métodos. Se incluyeron muestras de pacientes atendidos entre el 2005 y el 2007, y entre el 2014 y el 2016, en la unidad de hepatología de un hospital de Medellín. La genotipificación de las muestras se hizo mediante reacción en cadena de la polimerasa (Polymerase Chain Reaction, PCR) con análisis de los polimorfismos en la longitud de los fragmentos de restricción (Restriction Fragment Length Polymorphism, RFLP). Los resultados se compararon con los de dos grupos de control y con lo reportado en la base de datos del 1000 Genomes Project. Resultados. Se recolectaron 97 muestras de pacientes con diagnóstico de cirrosis y carcinoma hepatocelular. Los dos factores de riesgo más frecuentes fueron el consumo crónico de alcohol (18,6 %) y las colangiopatías (17,5 %). Los genotipos más frecuentes en la población de estudio fueron el ADH1B*1/1 (82 %), el ADH1C*1/1 (59 %) y el CYP2E1*C/C (84 %). Conclusiones. En este primer estudio de los polimorfismos en pacientes colombianos con diagnóstico de cirrosis y carcinoma hepatocelular, los genotipos más frecuentes fueron el ADH1B*1/1, el ADH1C*1/1 y el CYP2E1*C/C. No se observaron diferencias estadísticamente significativas en la frecuencia de los genotipos entre los casos y los controles. Se requieren estudios adicionales en población colombiana para evaluar el riesgo de la enfermedad hepática terminal por consumo crónico de alcohol y la asociación con los polimorfismos.
Introduction: One of the most important risk factors for hepatocellular carcinoma (HCC) is alcohol consumption: Studies in different populations suggest that the risk of liver disease could be associated with genetic variants of the enzymes involved in alcohol metabolism, such as alcohol dehydrogenase (ADH) and cytochrome P450 CYP2E1. Objective: To identify and characterize the allelic variants of ADH1B, ADH1C and CYP2E1 genes in Colombian patients with cirrhosis and/or HCC. Materials and methods: We included samples from patients attending the hepatology unit between 2005-2007 and 2014-2016 of a hospital in Medellin. Samples were genotyped using PCR-RFLP. We compared the results with two control groups and the 1000 Genomes Project database. Results: We collected 97 samples from patients with a diagnosis of cirrhosis and/or HCC. The two main risk factors were chronic alcohol consumption (18.6%) and cholangiopathies (17.5%). The most frequent genotypes in the study population were ADH1B*1/1 (82%), ADH1C*1/1 (59%), and CYP2E1*C/C (84%). Conclusions: This first study of polymorphisms in Colombian patients diagnosed with cirrhosis and/or HCC showed genotypes ADH1B*1/1, ADH1C*1/1 and CYP2E1*C/C as the most frequent. We found no significant differences in the genotype frequency between cases and controls. Further studies are necessary to explore the association between polymorphisms and the risk of end-stage liver disease from alcohol consumption.
Asunto(s)
Alcohol Deshidrogenasa , Citocromo P-450 CYP2E1 , Carcinoma Hepatocelular/etiología , Alelos , Genotipo , Cirrosis Hepática/etiologíaRESUMEN
OBJECTIVE: Combination vaccines have improved the efficiency of delivery of new vaccines in low and middle-income countries. Post-authorization monitoring of adverse events (AEs) after vaccination with a liquid pentavalent DTwP-HepB-Hib combination vaccine was conducted in Guatemalan infants. METHODS: A prospective observational safety study of the incidence of medical attended events (MAEs) and serious adverse events (SAEs) in children who received pentavalent and oral polio vaccines at 2, 4 and 6 months of age was conducted in two clinics at the Institute of Guatemala. Parents were contacted by telephone after each dose. All outpatient, emergency department visits, and hospitalizations were monitored. A self-controlled analysis was conducted to determine if there was evidence of increased risk of MAEs or SAEs following vaccines as compared to control time windows. RESULTS: Of 3000 recruited infants, 2812 (93.7%) completed the third dose and 2805 (93.5%) completed follow-up. Ten AEs in eight infants, of which four SAEs in four infants, were classified as related to the vaccine. Thirteen deaths were reported due to common illnesses of infancy, and none were judged to be related to the vaccine. The mortality rate (4.4 per 1000) was lower than expected for the population. The incidence-rate-ratio for healthcare visits was lower in post-vaccination time windows than for control windows; after the first vaccine dose, the rate ratios for the risk periods of 0-1, 2-6, and 7-30 days post-vaccination were 0.3, 0.5, and 0.7, respectively (all statistically significantly different from the reference value of 1.0 for the 31-60 day control period). CONCLUSION: The liquid pentavalent vaccine was associated with lower rates of health care visits and not associated with increases in SAEs or hospitalizations. Systems can be set up in low to middle income countries to capture all health care visits to monitor the safety of new vaccines.