Impact of immunoprophylaxis with palivizumab on respiratory syncytial virus infection in preterm infants less than 35 weeks in Colombian hospitals.

OBJECTIVE: To evaluate the impact of immunoprophylaxis with palivizumab in preterm infants less than 35 weeks in terms of hospitalization rate, intensive care unit requirement, and mortality. METHODS: A prospective cohort study was conducted at six Colombian hospitals. Preterm infants less than 35 weeks who received at least one dose of palivizumab during the first 6 months of life were included. The primary outcome was the hospitalization rate related to respiratory syncytial virus (RSV) infection. RESULTS: A total of 222 newborns participated in the study; 204 (91.8%) completed the 6-month follow-up, and three died during the study. 88.7% received a second dose of palivizumab, 79.7% a third, 34.7% a fourth, and 25.2% a fifth. The nonadjusted incidence rate of RSV infection was 2.4%, and the overall RSV-positive hospitalization rate was 1.9%. The proportion of patients that required Neonatal Intensive Care Unit (NICU) and mechanical ventilation in relation to RSV infection was 1.4%. Discharge with home oxygen, pulmonary dysplasia, and being younger than 6 months were significantly associated with respiratory infection. Furthermore, exposition to cigarette smoke was the only factor associated with increased risk of hospitalization. The group that required hospitalization received fewer doses of palivizumab (p = 0.049). No discontinuation of treatment due to adverse events were reported. No death was judged to be related to palivizumab. CONCLUSION: The hospitalization rate and the need for NICU admission were lower than those reported in the literature. In this real-life setting, palivizumab appears to be effective in preventing serious cases of RSV infection.

Incidence of external genital lesions related to human papillomavirus among Mexican men. A cohort study / Incidencia de lesiones genitales externas relacionadas con el virus del papiloma humano entre hombres mexicanos. Un estudio de cohorte

Abstract: Objective: To determine external genital lesion (EGL) incidence -condyloma and penile intraepithelial neoplasia (PeIN)- and genital HPV-genotype progression to these EGLs. Materials and methods: Participants (healthy males 18-74y from Cuernavaca, Mexico, recruited 2005-2009, n=954) underwent a questionnaire, anogenital examination, and sample collection every six months; including excision biopsy on suspicious EGL with histological confirmation. Linear array assay PCR characterized 37 high/low-risk HPV-DNA types. EGL incidence and cumulative incidence were calculated, the latter with Kaplan-Meier. Results: EGL incidence was 1.84 (95%CI=1.42-2.39) per 100-person-years (py); 2.9% (95%CI=1.9-4.2) 12-month cumulative EGL. Highest EGL incidence was found in men 18-30 years: 1.99 (95%CI=1.22-3.25) per 100py. Seven subjects had PeIN I-III (four with HPV16). HPV11 most commonly progresses to condyloma (6-month cumulative incidence=44.4%, 95%CI=14.3-137.8). Subjects with high-risk sexual behavior had higher EGL incidence. Conclusion: In Mexico, anogenital HPV infection in men is high and can cause condyloma. Estimation of EGL magnitude and associated healthcare costs is necessary to assess the need for male anti-HPV vaccination.

Resumen: Objetivo: Determinar incidencia de lesiones genitales externas (LGE) -condiloma y neoplasia intraepitelial del pene (NIP)- y progresión de genotipos de VPH a LGE. Material y métodos: Se aplicaron cuestionarios, examen anogenital y recolección de muestras cada seis meses a hombres sanos (18-74 años, de Cuernavaca, México, reclutados 2005-2009, n=954) con biopsia y confirmación histológica. Se caracterizaron 37 tipos de ADN-VPH; se calculó incidencia de LGE (cumulativa con Kaplan-Meier). Resultados: Incidencia de LGE=1.84 (IC95%=1.42-2.39) por 100-persona-años (pa); 2.9% (IC95%=1.9-4.2) LGE acumulativa a 12 meses. Mayor incidencia de LGE entre hombres 18-30 años; 1.99 (IC95%=1.22-3.25) por 100pa. Siete sujetos tuvieron NIP I-III. VPH-11 más comúnmente progresa a condiloma (incidencia acumulativa a seis meses=44.4%, IC95%=14.3-137.8). Los sujetos con comportamiento sexual de alto riesgo tuvieron mayor incidencia de LGE. Conclusiones: En México la infección anogenital con VPH es alta y puede causar condiloma. La estimación de magnitud de LGE y los costos sanitarios asociados se necesita para evaluar la necesidad de vacunación contra VPH en hombres.

Prevalence and incidence of anal human papillomavirus infection in Mexican men: Need for universal prevention policies / Prevalencia e incidencia de infección por virus de papiloma humano en canal anal en hombres mexicanos: Necesidad de políticas de prevención universal

Abstract: Objective: Describe the natural history of anal HPV among men. Materials and methods: Prospective study among men 18-70 years (n=665), from Cuernavaca, Mexico who completed questionnaires and provided specimens (HPV genotyped) at enrollment and 1+ follow-up visit. HPV prevalence and incidence were estimated. Prevalence ratios were calculated with Poisson regression using robust variance estimation. Person-time for incident HPV infection was estimated using number of events modeled as Poisson variable for total person-months. Results: Anal infection prevalence: any HPV type=15%, high-risk=8.4%, HPV16=1.4%, tetravalent vaccine types (4vHPV)=4.4%, nonavalent vaccine types (9vHPV)=6.3%. Factors associated with prevalence: 50+ lifetime female sex partners (adjusted prevalence ratio, a PR=3.25, 95% CI:1.12-9.47), 10+ lifetime male sex partners (aPR=3.06, 95%CI:1.4-6.68), and 1+ recent male anal sex partners (aPR=2.28, 95%CI:1.15-4.5). Anal incidence rate: high-risk HPV=7.8/1 000 person-months (95%CI:6.0-10.1), HPV16=1.8/1 000 person-months (95%CI:1.1-2.9),4vHPV=3.4/1 000 person-months (95%CI:2.3-4.9) and 9vHPV=5.5/1000 person-months (95%CI:4.1-7.5). Conclusions: Implementation of universal HPV vaccination programs, including men, is a public health priority.

Resumen: Objetivo: Generar evidencia que apoye la vacunación universal contra VPH. Material y métodos: Estudio prospectivo con hombres 18-70 años (n=665) de Cuernavaca, México con cuestionarios y genotipificación de VPH en muestras (2+mediciones). Se estimó prevalencia e incidencia; se calcularon tasas de prevalencia con regresión Poisson. Se estimó persona-tiempo para infecciones incidentes. Resultados: Prevalencia de infección anal: cualquier tipo de VPH=15%, alto-riesgo=8.4%, VPH16=1.4%, tipos en vacuna tetravalente=4.4% y tipos en vacuna nonavalente=6.3%. Factores asociados con infección prevalente: 50+ parejas sexuales femeninas en la vida (tasa de prevalencia ajustada, TPa=3.25, IC95%:1.12-9.47); 10+ parejas sexuales masculinas en la vida (TPa=3.06, IC95%:1.4-6.68) y 1+ parejas masculinas (sexo anal) recientes (TPa=2.28, IC95%:1.15-4.5). Tasas de incidencia para infección anal: VPH alto-riesgo=7.8/1000 persona-meses (IC95%:6.0-10.1), VPH 16=1.8/1000 persona-meses (95%IC:1.1-2.9), tipos en vacuna tetravalente=3.4/1000 persona-meses y tipos en vacuna nonavalente=5.5/1000 persona-meses. Conclusiones: Implementación de programas de vacunación universal (incluyendo hombres) contra VPH es una prioridad en salud pública.

Incidence of external genital lesions related to human papillomavirus among Mexican men. A cohort study.

OBJECTIVE: To determine external genital lesion (EGL) incidence -condyloma and penile intraepithelial neoplasia (PeIN)- and genital HPV-genotype progression to these EGLs. MATERIALS AND METHODS: Participants (healthy males 18- 74y from Cuernavaca, Mexico, recruited 2005-2009, n=954) underwent a questionnaire, anogenital examination, and sample collection every six months;including excision biopsy on suspicious EGL with histological confirmation.Linear array assay PCR characterized 37 high/low-risk HPV-DNA types. EGL incidence and cumulative incidence were calculated, the latter with Kaplan-Meier. RESULTS: EGL incidence was 1.84 (95%CI=1.42-2.39) per 100-person-years (py); 2.9% (95%CI=1.9-4.2) 12-month cumulative EGL.Highest EGL inci- dence was found in men 18-30 years:1.99 (95%CI=1.22-3.25) per 100py. Seven subjects had PeIN I-III (four with HPV16). HPV11 most commonly progresses to condyloma (6-month cumulative incidence=44.4%, 95%CI=14.3-137.8). Subject with high-risk sexual behavior had higher EGL incidence. CONCLUSIONS: In Mexico, anogenital HPV infection in men is high and can cause condyloma. Estimation of EGL magnitude and associated healthcare costs is necessary to assess the need for male anti-HPV vaccination.

OBJETIVO: Determinar incidencia de lesiones genitales externas (LGE) ­condiloma y neoplasia intraepitelial del pene (NIP)­ y progresión de genotipos deVPH a LGE. MATERIAL Y MÉTODOS: Se aplicaron cuestionarios,examen anogenital y recolección de muestras cada seis meses a hombres sanos (18-74 años, de Cuernavaca, México, reclutados 2005-2009, n=954) con biopsia y confirmación histológica. Se caracteri- zaron 37 tipos de ADN-VPH; se calculó incidencia de LGE (cumulativa con Kaplan-Meier). RESULTADOS: Incidencia de LGE=1.84 (IC95%=1.42-2.39) por 100-persona-años (pa); 2.9% (IC95%=1.9-4.2) LGE acumulativa a 12 meses. Mayor incidencia de LGE entre hombres 18-30 años; 1.99 (IC95%=1.22-3.25) por 100pa.Siete sujetos tuvieron NIP I-III. VPH-11 más comúnmente progresa a condiloma (incidencia acumulativa a seis meses=44.4%, IC95%=14.3-137.8). Los sujetos con comportamiento sexual de alto riesgo tuvieron mayor incidencia de LGE. CONCLUSIONES: En México la infección anogenital conVPH es alta y puede causar condiloma. La estimación de magnitud de LGE y los costos sanitarios asociados se necesita para evaluar la necesidad de vacunación contra VPH en hombres.

Prevalence and incidence of anal human papillomavirus infection in Mexican men: Need for universal prevention policies.

OBJECTIVE: Describe the natural history of anal HPV among men. MATERIALS AND METHODS: Prospective study among men 18-70 years (n=665), from Cuernavaca, Mexico who completed questionnaires and provided specimens (HPV genotyped) at enrollment and 1+ follow-up visit. HPV prevalence and incidence were estimated. Prevalence ratios were calculated with Poisson regression using robust variance estimation. Person-time for incident HPV infection was estimated using number of events modeled as Poisson variable for total person-months. RESULTS: Anal infection prevalence: any HPV type=15%, high-risk=8.4%, HPV16=1.4%, tetravalent vaccine types (4vHPV)=4.4%, nonavalent vaccine types (9vHPV)=6.3%. Factors associated with prevalence: 50+ lifetime female sex partners (adjusted prevalence ratio, a PR=3.25, 95% CI:1.12- 9.47), 10+ lifetime male sex partners (aPR=3.06, 95%CI:1.4- 6.68), and 1+ recent male anal sex partners (aPR=2.28, 95%CI:1.15-4.5). Anal incidence rate: high-risk HPV=7.8/1000 person-months (95%CI:6.0-10.1), HPV16=1.8/1000 personmonths (95%CI:1.1-2.9),4vHPV=3.4/1000 person-months (95%CI:2.3-4.9) and 9vHPV=5.5/1000 person-months (95%CI:4.1-7.5). CONCLUSIONS: Implementation of universal HPV vaccination programs, including men, is a public health priority.

OBJETIVO: Generar evidencia que apoye la vacunación universal contra VPH. MATERIAL Y MÉTODOS: Estudio prospectivo con hombres 18-70 años (n=665) de Cuernavaca, México con cuestionarios y genotipificación de VPH en muestras (2+mediciones). Se estimó prevalencia e incidencia; se calcularon tasas de prevalencia con regresión Poisson. Se estimó persona-tiempo para infecciones incidentes. RESULTADOS: Prevalencia de infección anal: cualquier tipo de VPH=15%, altoriesgo=8.4%, VPH16=1.4%, tipos en vacuna tetravalente=4.4% y tipos en vacuna nonavalente=6.3%. Factores asociados con infección prevalente: 50+ parejas sexuales femeninas en la vida (tasa de prevalencia ajustada, TPa=3.25, IC95%:1.12-9.47); 10+ parejas sexuales masculinas en la vida (TPa=3.06, IC95%:1.4- 6.68) y 1+ parejas masculinas (sexo anal) recientes (TPa=2.28, IC95%:1.15-4.5). Tasas de incidencia para infección anal: VPH alto-riesgo=7.8/1000 persona-meses (IC95%:6.0-10.1), VPH 16=1.8/1000 persona-meses (95%IC:1.1-2.9), tipos en vacuna tetravalente=3.4/1000 persona-meses y tipos en vacuna nonavalente=5.5/1000 persona-meses. CONCLUSIONES: mplementación de programas de vacunación universal (incluyendo hombres) contra VPH es una prioridad en salud pública.

Distribución de los genotipos del virus del papiloma humano en mujeres de Bogotá con anomalías en la citología cervicouterina / Genotype distribution of Human Papillomavirus in women from Bogotá with abnormal cervical smear

Objetivos: Determinar la distribución de los genotipos de VPH en mujeres de Bogotá con citología cervicouterina anormal. Métodos: Se colectaron muestras cervicales de 191 mujeres con ASCUS, 236 con lesiones intraepiteliales escamosas de bajo grado (LIEBG) y 116 de alto grado (LIEAG). La tipificación de VPH se realizó usando PCR con iniciadores consenso GP5+/GP6+ y reverse line blot. Resultados: La prevalencia de VPH fue 76,1%. Se observaron infecciones únicas en el 41,4% de las participantes, y coinfecciones en el 34,6%. La frecuencia de VPH según diagnóstico fue: 60,2%, 84,7% y 84,5% en ASCUS, LIEBG y LIEAG. Los VPH-16 y 58 fueron los tipos más frecuentes en los tres grupos, con frecuencias para VPH-16 de 20,4%, 33,9% y 38,8%, y para VPH-58 de 7,3%, 13,6%, 18,1% para ASCUS, LIEBG y LIEAG. En ASCUS y LSIL el tercer tipo en frecuencia fue VPH-56 (6,8% y 11,0%), mientras que en LIEAG fue VPH-18 (10,3%). Las infecciones con tipos virales probablemente oncogénicos y con tipos de bajo riesgo fueron mucho menos frecuentes y en general se presentaron como coinfecciones con tipos de alto riesgo. Conclusiones: Las infecciones con tipos de VPH de alto riesgo fueron las más frecuentes en todas las lesiones estudiadas, el VPH-58 ocupo el segundo lugar en frecuencia, como ha sido reportado en México y en general en Suramérica. El cambio hacia nuevas vacunas profilácticas que incluyan más tipos virales como el VPH-58 puede tener un mayor impacto en la disminución de la incidencia de lesiones preneoplásicas en nuestra región.

Objective: To determine the distribution of HPV genotypes in women from Bogotá with abnormal cervical smear. Methods: Cervical samples were collected from 191 women with ASCUS, 236 with low-grade (LSIL) and 116 with high-grade squamous intraepithelial lesions (HSIL). HPV typing was performed using consensus PCR primers GP5+/GP6 + and reverse line blot. Results: The prevalence of HPV was 76.1%. Unique infections were observed in 41.4% of the participants and co-infections in 34.6%. The frequency of HPV according to diagnosis was: 60.2%, 84.7% and 84.5% in ASCUS, LSIL and HSIL respectively. HPV16 and 58 were the more frequent types in the three groups, HPV16 frequencies were 20.4%, 33.9% and 38.8%, and HPV58 frequencies were 7.3%, 13.6%, and 18,1% for ASCUS, LSIL and HSIL respectively. The third type in frequency in ASCUS and LSIL was HPV56 (6.8% and 11.0%), while in HSIL was HPV18 (10.3%). Infections with probably oncogenic types or with low risk types were much less frequent and generally were observed as co-infections with high-risk types. Conclusions: Infections with high risk HPV types were the most frequent in all studied lesions, VPH-58 ranked second in frequency as has been reported in Mexico and in general in South America. The change to new prophylactic vaccines including more viral types as HPV58 could have a higher impact in reducing the incidence of pre-neoplastic lesions in our region.

Fractales: ayuda diagnóstica para células preneoplásicas y cancerígenas del epitelio escamoso cervical confirmación de aplicabilidad clínica / Fractals: diagnostic help for preneoplastic and canceriginal cells of cervical scalpal epithelium confirmation of clinical applicability / Fractales: ajuda diagnóstica para células preneoplásticas e canceriginas do epitelio do scalpel cervical confirmação da aplicabilidade clínica

Antecedentes: Se desarrolló un método diagnóstico fractal para evaluar células del cuello uterino utilizando el concepto de Armonía Matemática Intrínseca (AMI) y variabilidad celular, el cual diferencia matemáticamente células normales de células L-SIL y H-SIL, haciendo innecesario el diagnóstico de células ASCUS. Objetivo: confirmar la capacidad diagnóstica de la metodología desarrollada mediante un estudio ciego de comparación con el Gold Standard. Método: se tomaron fotografías digitales de 50 preparaciones citológicas de mujeres entre 20 y 55 años: 5 con diagnóstico de citología normal y 45 con diferentes grados de lesión hasta carcinoma, incluyendo 5 ASCUS. Se calculó la dimensión fractal de tres objetos matemáticos: núcleo, citoplasma y totalidad, a partir de la superposición de cinco rejillas. Además, se evaluó su dimensión fractal mediante el concepto de AMI y variabilidad celular. Los resultados obtenidos se compararon con el diagnóstico citopatológico convencional determinando su sensibilidad, especificidad y coeficiente kappa. Resultados: La sensibilidad y especificidad fue del 100%, y el coeficiente Kappa de 1. Conclusiones: Los resultados en una población diferente a la inicial son una evidencia de la capacidad de esta metodología para diagnosticar objetiva y cuantitativamente células normales, L-SIL y H-SIL, así como aclarar el diagnóstico de las células ASCUS con base en la dimensión fractal y el concepto de AMI y variabilidad.

Introduction: A new fractal diagnostic method was applied for assessing cervix cells using the Intrinsic Mathematical Harmony (IMH) concept and cellular variability, which mathematically differentiates normal, L-SIL and H-SIL cells making unnecessary the diagnostic of ASCUS cells. Objective: To confirm the diagnostic capability of developed methodology by a blind study of comparison with Gold Standard. Methods: Digital pictures were taken of 50 cells from cytology of 20 to 55 year-old women; 5 with normal diagnosis and 45 with several lesion degrees until carcinoma, including 5 with ASCUS diagnosis. Fractal dimension of three mathematical objects was calculated by superposing five grids: nucleus, cytoplasm and totality. Moreover, their fractal dimension was assessed through the Intrinsic Mathematical Harmony concept and cellular variability. The obtained diagnosis was compared with conventional cytopathologic diagnosis determining sensibility, specificity and Kappa coefficient. Results: 100% Sensibility and specificity, and a Kappa Coefficient of 1 were obtained. Conclusions: The results, in a population different to the initial one, are an evidence of the ability of this methodology for objectively and quantitatively diagnosing the normal, L-SIL and H-SIL cells, as well as for clarifying the ASCUS cells diagnosis, based on fractal dimension and IMH concept and variability.

Introdução: Um novo método de diagnóstico fractal foi aplicado para avaliar as células do colo do útero usando conceito intrínseco harmonia matemática (IMH) e variabilidade celular, que normalmente diferencia matematicamente, LSIL e HSIL células que fazem o diagnóstico de células desnecessários ASCUS. Objetivo: Para confirmar a capacidade de diagnóstico da metodologia desenvolvida por um estudo cego de comparação com Gold Standard. Métodos: Foram tiradas fotos digitais de 50 células de citologia de mulheres com 20 a 55 anos de idade; 5 com diagnóstico normal e 45 com vários graus de lesão até carcinoma, incluindo 5 com diagnóstico de ASCUS. A dimensão fractal de três objetos matemáticos foi calculada através da superposição de cinco grades: núcleo, citoplasma e totalidade. Além disso, sua dimensão fractal foi avaliada através do conceito de harmonia matemática Intrínseca e da variabilidade celular. O diagnóstico obtido foi comparado com o diagnóstico citopatológico convencional, determinando a sensibilidade, especificidade e coeficiente Kappa. Resultados: Foram obtidos 100% de sensibilidade e especificidade e um Coeficiente Kappa de 1. Conclusões: Os resultados, em uma população diferente da inicial, são uma evidência da habilidade desta metodologia para o diagnóstico objetivo e quantitativo das células normais, L-SIL e H-SIL, bem como para esclarecer o diagnóstico das células ASCUS, Baseado na dimensão fractal e no conceito e variabilidade de IMH.

Presencia y persistencia de variantes moleculares del ORF E6 y ORF E7 del VPH 58 en mujeres con citología normal que pertenecen a la cohorte de Bogotá, Colombia / Presence and persistence of HPV 58 molecular variations ORF E6 and ORF E7 among women with normal cytology in the Bogotá, Colombia cohort

Objetivo: Analizar la presencia y persistencia de variantes en E6/E7/VPH 58 en muestras de mujeres con infecciones prevalentes por VPH 58, con citología normal, que pertenecen a la cohorte de Bogotá, Colombia. Métodos: Se utilizaron cepillados cervicales de 34 mujeres VPH 58, con citología normal, pertenecientes a la línea de base de la cohorte, con su respectivo seguimiento. Se amplificó la región E6/E7 del VPH 58 usando los iniciadores E6F1-E7R1 y los iniciadores E7P1-E7P2. Para el análisis de las variantes se utilizó la técnica de secuencia automática directa. La secuencia referencia del VPH 58 se utilizó para comparar las secuencias obtenidas. Resultados: En 27/34 muestras se lograron detectar variantes de E6/E7 de VPH 58. En total, se detectaron cinco variantes diferentes, dos de ellas nunca antes reportadas (A169/T307/A694/G744/A761 y T307/A694/G744/A761/G763). Los análisis de eliminación mostraron que el 75% de las variantes se habían eliminado antes de los dos años de seguimiento, y todas las variantes ya se habían eliminado a los seis años de seguimiento. Conclusiones: Dos nuevas variantes se reportaron a escala mundial de gran relevancia en los ámbitos filogenético y epidemiológico.

Objective: To analyze the presence and persistence of E6/E7 HPV58 variations in women with prevalent HPV 58 infection, with normal cytology, who belong to the Bogotá, Colombia cohort. Methods: Cervical cytobrush was used on 34 HPV58 women, with normal cytology, who are part of the cohort base line; respective follow was performed. The HPV58 E67/E7 region was broadened by using E6F1-E7R1 and E7P1-E7P2 indicators. Variation analysis was carried out with automatic direct sequencing. HPV58 sequence reference was used to compare the sequences that had been obtained. Results: In 27/34 samples, E6/E7 variations of HPV58 were successfully detected. A total of five different variations were detected, two of which had never been reported before (A169/T307/A694/G744/A761 and T307/A694/G744/A761/G763). Elimination analysis revealed that 75% of variations had been eliminated within two years of follow up, and that all variation had been eliminated at the end of six years of follow up. Conclusions: Two new variations of universal phylogenetic and epidemiologic noteworthiness were reported.

Actividad de la telomerasa e infección por VPH en raspados cervicales de mujeres que desarrollaron lesiones escamosas intraepiteliales de alto grado: un estudio de seguimiento / Telomerase activity and HPV infection in cervical smears of women with high grade squamous intraephitelial lesions: a follow-up study

Objetivo: Describir la AT y la infección por VPH en el seguimiento de mujeres que pertenecen a la cohorte de Bogotá. Métodos: Se analizaron 79 muestras del seguimiento de 25 mujeres que desarrollaron LEI-AG y 149 muestras del seguimiento de 34 mujeres con citología normal. La detección del VPH se realizó usando PCR-EIA GP5+/GP6+ y RLB. La AT se midió mediante TRAP-ELISA. Resultados: El análisis mostró que de los 25 casos, 8 fueron casos prevalentes (ingresaron al estudio con la LEI-AG) y los 17 casos restantes fueron incidentes (la lesión se detectó durante el seguimiento). De estas 17 mujeres, 12 (70,5%) presentaron AT y VPH al momento del diagnóstico o en una visita previa, con VPH de alto riesgo (VPH-AR), principalmente de la especie α-9. Tres mujeres (17,7%) mostraron infecciones transitorias por VPH y 2 (11,8%) no tuvieron VPH o AT al diagnóstico. El seguimiento de la mujeres con citología normal mostró que solo ocho mujeres tuvieron VPH y AT al mismo tiempo (23,5%), 21/34 mujeres (61,8%) tuvieron eventos transitorios de VPH durante el seguimiento y 5 (14,7%) no tuvieron VPH durante todo el seguimiento. Conclusiones: Detectar AT e infección por VPH-AR al mismo tiempo parecen predecir el riesgo de LEI-AG.

Objective: To describe telomerase activity (TA) and HPV infection in follow up of women in the Bogotá cohort. Methods: Analysis was carried out on 79 follow up samples from 25 women who developed LEI-AG, and 149 follow up samples from 34 women with normal cytology. HPV detection was made with PCR-EIA GP5+/GP6+ and RLB. TA was measured with TRAP-ELISA. Results: Analysis revealed that out of the 25 cases, 8 were prevalent (enrolled in the study with LEI-AG), and the remaining 17 incidental (lesion was detected during follow up). Among these 17 women, 12 (70.5%) had, at diagnosis or during a previous checkup, TA and high-risk HPV (HPV-AR), primarily type α-9. Three women (17.7%) had transitory HPV infections, and 2 (11.8%) had neither HPV nor TA at diagnosis. Follow up on women with normal cytology revealed that only eight women (23.5%) had HPV and TA at the same time, 21/34 women (61.8%) had transitory HPV event during follow up, and 5 (14.7%) had no HPV during entirety of follow up. Conclusions: Detection of TA and simultaneous HPV-AR infection apparently predicts LEI-AR risk.

Determinantes de la regresión de lesiones cervicales de bajo grado en una cohorte de mujeres colombianas / Determinants of LSIL regression in women from a colombian cohort

Objective: To analyze the role of Human Papillomavirus (HPV) and other risk factors in the regression of cervical lesions in women from the Bogotá Cohort. Methods: 200 HPV positive women with abnormal cytology were included for regression analysis. The time of lesion regression was modeled using methods for interval censored survival time data. Median duration of total follow-up was 9 years. Results: 80 (40%) women were diagnosed with Atypical Squamous Cells of Undetermined Significance (ASCUS) or Atypical Glandular Cells of Undetermined Significance (AGUS) while 120 (60%) were diagnosed with Low Grade Squamous Intra-epithelial Lesions (LSIL). Globally, 40% of the lesions were still present at first year of follow up, while 1.5% was still present at 5 year check-up. The multivariate model showed similar regression rates for lesions in women with ASCUS/AGUS and women with LSIL (HR= 0.82, 95% CI 0.59-1.12). Women infected with HR HPV types and those with mixed infections had lower regression rates for lesions than did women infected with LR types (HR=0.526, 95% CI 0.33-0.84, for HR types and HR=0.378, 95% CI 0.20-0.69, for mixed infections). Furthermore, women over 30 years had a higher lesion regression rate than did women under 30 years (HR= 1.53, 95% CI 1.03-2.27). The study showed that the median time for lesion regression was 9 months while the median time for HPV clearance was 12 months. Conclusions: In the studied population, the type of infection and the age of the women are critical factors for the regression of cervical lesions.

Objetivo: Analizar el papel del virus del papiloma humano (VPH) y otros factores en la regresión de lesiones del cuello del útero en mujeres de la cohorte de Bogotá, Colombia. Métodos: El tiempo medio de seguimiento fue nueve años. Se incluyeron 200 mujeres VPH positivas con citología anormal. El tiempo de regresión de lesión fue modelado mediante análisis de supervivencia censurando por intervalos. Resultados: 80 mujeres (40%) tuvieron células escamosas atípicas de significado indeterminado (ASCUS) o células glandulares atípicas de significado indeterminado (AGUS) y 120 (60%) tuvieron lesiones escamosas intraepiteliales de bajo grado (LEI-BG). El 40% de las lesiones estaban presentes en el primer año de seguimiento, mientras que el 1,5% aún estaba a los cinco años. Se observaron tasas similares de regresión para ASCUS/AGUS y LEI-BG (HR=0,82, IC 95% 0,59-1,12). Mujeres infectadas con VPH de alto riesgo y aquéllas con infecciones mixtas tuvieron tasas inferiores de regresión de las lesiones que las mujeres con VPH de bajo riesgo (HR=0,526, IC 95% 0,33-0,84, para los VPH de alto riesgo, y HR=0,378, IC 95% 0,20-0,69, para las infecciones mixtas). Las mujeres mayores de 30 años tuvieron una mayor tasa de regresión de lesiones que las menores de 30 (HR= 1,53, IC 95% 1,03-2,27). El tiempo medio de regresión de las lesiones fue 9 meses, y el tiempo medio para la eliminación del VPH fue 12 meses. Conclusiones: En la población estudiada, el tipo de infección y la edad de las mujeres son factores críticos para la regresión de lesiones cervicales.

Generalización fractal de células preneoplásicas y cancerígenas del epitelio escamoso cervical: una nueva metodología de aplicación clínica / Fractal generalization of pre-neoplasic cervical epithelial cells for clinical application / Generalização fractal de célula pré-neoplásicas e cancer do epitélio escamoso cervical: uma nova metodologia de aplicação clínica

A partir de la evaluación de las dimensiones fractales y aplicando el concepto de variabilidad y armonía matemática intrínseca celular (AMI), se desarrolló un método matemático de aplicación clínica para el diagnóstico de células preneoplásicas y neoplásicas del epitelio escamoso cervical, el cual supera el diagnóstico de ASCUS (células escamosas atípicas de significado no determinado). A partir de un método desarrollado previamente para el diagnóstico de células normales, ASCUS y L-SIL, se realizaron permutaciones estructurales fractales con los valores generales de la AMI y de variabilidad fractal para normalidad y enfermedad, buscando los prototipos generales de células normales, preneoplásicas y neoplásicas. Se midieron cinco células ASCUS y cinco cancerígenas del epitelio escamoso del cuello uterino y se encontró que para la normalidad hay 18 prototipos, mientras que para la anormalidad 44, incluyendo todos los estados de evolución hasta carcinoma. Estos resultados fueron confirmados al comparar los resultados obtenidos por las técnicas convencionales con los obtenidos por esta metodología; lo que hace pensar que se desarrolló una nueva metodología que permite diferenciar los distintos tipos de células del epitelio escamoso del cuello uterino (normales o cancerígenas)...

Beginning with the evaluation of fractal dimensions, and applying the concept of variability and Cellular Intrinsic Mathematical Harmony, a mathematical method for clinical application was developed, about the diagnosis of preneoplastic and neoplastic squamous epithelial cervix cells, which improves the ASCUS (Atypical Squamous Cells of Undetermined Significance) diagnosis. Beginning with a method previously developed for the diagnosis of normal, ASCUS and L-SIL cells, fractal structural permutations with the general Intrinsic Mathematical Harmony (IMH) and variability values for normality and disease were made, looking for the general prototypes of normal cells, premalignant and carcinogen. 5 ASCUS and 5 carcinogen cells of the squamous epithelial cervix were measured. It was found that there are 18 normal prototypes, while there were obtained 44 prototypes for the abnormality, including all stages of evolution to carcinoma. These results were confirmed by comparing the obtained results by the conventional techniques with the results obtained by this methodology; making thinking that it was developed a new methodology that allows to differentiate the distinct types of the squamous epithelial cervix cells (normal or carcinogen)...

A partir da avaliaçúo da dimensúo fractal e aplicação do conceito de variabilidade e harmonia matemática subjacente celular (IAM), desenvolveu-se um método matemático para a aplicação clínica o diagnóstico de células pré-neoplásicas e neoplásicas do epitélio escamoso cervical, o que excede o diagnóstico ASCUS (células escamosas atípicas de significado indeterminado). Baseado em um método desenvolvido anteriormente para o diagnóstico de células normais, ASCUS e LSIL, foram realizadas permutações estruturais fractais com os valores gerais da AMI e variabilidade fractal para o normal e doença, procurando protótipos gerais de células normais, pré-neoplásicas e neoplásicas. Foram medidos cinco células ASCUS e cinco de câncer de epitélio escamoso cervical e encontrou-se que existem para o normal 18 protótipos, enquanto que para a alteração 44, incluindo todas as fases de evoluçúo para carcinoma. Estes resultados foram confirmados através da comparação dos resultados obtidos por técnicas convencionais com aqueles obtidos por este modelo matemático, sugerindo que desenvolveu-se uma nova metodologia para diferenciar diferentes tipos de células do epitélio escamoso cervical (normais ou cancerosos)...

Impacto de una política de restricción de uso de antibióticos en la unidad neonatal del Hospital Militar Central / Impacto de uma politica de restrição de uso de antibióticos na unidade neonatal do Hospital Militar Central de Bogota / The impact of an antibiotic restriction policy in the intensive care unit at the Hospital Militar Central

Teniendo en cuenta que el uso indiscriminado de antibióticos de amplio espectro ha favorecido la aparición de resistencia bacteriana a múltiples drogas, se realizó un estudio de intervención cuasiexperimental entre enero de 2002 y enero de 2006 en la unidad de cuidados intensivos neonatal (UCIN) del Hospital Militar Central de Bogotá (HMC), en el que se restringió el uso de cefalosporinas de 3ª generación cambiándolas por antibióticos no asociados con inducción de beta-lactamasas de espectro extendido (BLEEs), utilizando piperazilina-tazobactam y cefepime. En el estudio se hizo comparación antes y después de la política de restricción antibiótica en infecciones nosocomiales por gérmenes gram negativos, encontrándose que de 2880 pacientes que ingresaron a UCIN, el 24,5% tuvo diagnóstico de infección y de ellos, el 30,7% correspondió a infecciones hospitalarias. De los gérmenes aislados el 49% correspondió a bacterias gram negativas, con una producción de BLEEs en el 51% de los aislados de Klebsiella pneumoniae, de 28% en los de Escherichia coli, de 14% en los de Acinetobacter baumannii y de 7% en los de Serratia. En el 70% de los casos con presencia de BLEEs se habían utilizado cefalosporinas de III generación. Luego de la restricción de cefalosporinas de III generación se observó una importante disminución en los aislamientos de los gérmenes productores de resistencia betalactámica (del 20% en el primer periodo, se bajó a menos del 4% en el segundo), es decir que el riesgo producir BLEEs disminuyó casi cinco veces, con una razón de prevalencia de 4,91(IC 95%: 1,14-21,09) y un valor de p=0,031 respecto al periodo anterior, pudiéndose concluir que la adopción de una política de restricción en el uso de antibióticos tuvo un significativo efecto reductor en la incidencia de BLEEs en la UCIN de nuestro hospital, disminuyendo a su vez los costos, pues se redujo el uso de carbapenems...

Considering that the indiscriminate use of wide spectrum antibiotics has favour the appearance of bacterial resistance to multiple drugs, a quasi-experiemental intervention study was performed between January 2002 and January 2006, in the neonatal intensive care unit (NICU) of the Hospital Militar Central in Bogotá (HMC), in which the use of cephalosporins of 3th generation was restricted and changed for antibiotics non associated with the induction of beta-lactamases of extended spectrum (ESBLs), by the use of piperacillin-tazobactam and cefepime. A comparison was done before and after the restriction policy was applied in nosocomial infections produced by gram-negative bacteria. It was found that 24, 5% out of 2880 patients were diagnose with infections and among them, 30,7% were nosocomial infection. 49% of isolated germs were Gram-negative bacteria from which 51% of Klebsiella pneumoniae, 28% of Escherichia coli, 14% of Acinetobacter baumannii and 7% of Serratia isolates produced ESBLs. In 70% of the ESBLs cases, cephalosporins of 3er generation were used. After restriction of cephalosporins of 3 th generation an important decreased in the number of beta-lactamic resistance isolates were observed (from 20% during the first period to less than 4 % during the second), which means that the risk of ESBLs production decreased five times, with a ratio of prevalence of 4,91 (IC 95%: 1,14-21,09) and a p value of 0,031 with respect to the previous period. It can be conclude that the adoption of a restriction policy in the use of antibiotics had a significant reductor effect on the incidence of ESBLs in NICU of our Hospital, which implies a reduction of costs as the use of carbapenems was also reduced...

Tendo em conta que o uso indiscriminado de antibióticos de amplo espectro favoreceu a aparição de resistência bacteriana a numerosos medicamentos, realizou-se um estudo de intervenção experimental entre janeiro de 2002 e janeiro de 2006 na unidade de terapia intensivos neonatal (UTIN) do Hospital Militar Central de Bogotá, no que se restringiu o uso de cefalosporinas de III geração mudando-as por antibióticos não associados com indução de beta-lactamasas de espectro estendido (BLEEs), utilizando piperazilina-tazobactam e cefepime. No estudo se fez comparação antes e depois da política de restrição antibiótica em infecções nosocomiais por bactérias gram negativos, encontrando-se que de 2880 pacientes que ingressaram a UTIN, o 24,5% teve diagnóstico de infecção e deles, o 30,7% correspondeu a infecções hospitalares. Dos germens isolados o 49% correspondeu a bactérias gram negativas, com uma produção de BLEEs no 51% dos isolados de Klebsiella, de 28% nos de Escherichia coli, de 14% nos de Acinetobacter e de 7% nos de Serratia. No 70% dos casos com presença de BLEEs se tinham utilizado cefalosporinas de III geração. Depois da restrição de cefalosporinas de III geração se observou uma importante diminuição nos isolamentos dos germes produtores de resistência beta-lactámica (do 20% no primeiro período, baixou-se a menos do 4% no segundo), isto é que o risco produzir BLEEs diminuiu quase cinco vezes, com uma razão de prevalência de 4,91(IC 95%: 1,14-21,09) e um valor de p=0,031 com respeito ao período anterior, podendo-se concluir que a adoção de uma política de restrição no uso de antibióticos teve um significativo efeito redutor na incidência de BLEEs na UTIN de nosso hospital, diminuindo a sua vez os custos, pois se reduziu o uso de carbapenems...

Smoking and human papillomavirus infection: pooled analysis of the International Agency for Research on Cancer HPV Prevalence Surveys.

BACKGROUND: Smoking increases the risk of squamous-cell carcinoma of the cervix, but it is not clear whether smoking increases the risk of acquisition or persistence of human papillomavirus (HPV) infection. METHODS: Information on smoking was collected from 10 areas in four continents among population-based, age-stratified random samples of women aged 15 years or older. HPV testing was performed using PCR-based enzyme immunoassay. Unconditional logistic regression was used to estimate odds ratios (OR) and corresponding 95% confidence intervals (CI) of being HPV-positive by smoking habits, adjusted for age and lifetime number of sexual partners. RESULTS: Ten thousand five hundred and seventy-seven women (mean age 41.4 years) were included. Among current smokers, the risk of being HPV-positive increased with smoking intensity, after allowing for lifetime number of sexual partners: ORs for <5, 5-14 and >/=15 cigarettes per day were 1.21 (95% CI 0.95-1.54), 1.39 (95% CI 1.04-1.87) and 2.01 (95% CI 1.32-3.08), respectively, as compared with never-smokers. The risk among former smokers (OR = 0.95, 95% CI 0.73-1.23) was similar to that among never-smokers. Analyses stratified by lifetime number of sexual partners showed a significant trend in risk only for women with one lifetime sexual partner. CONCLUSIONS: Our study suggests that current, though not former, smoking is associated with an increased prevalence of HPV, after allowance for sexual covariates. Among current smokers, HPV prevalence increased with smoking intensity, but a clear dose-response relationship was exclusively seen among women who declared one lifetime sexual partner.

Cervical infection with Chlamydia trachomatis and Neisseria gonorrhoeae in women from ten areas in four continents. A cross-sectional study.

OBJECTIVES: Better information on the prevalence of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infection is needed in many world areas. STUDY DESIGN: Cross-sectional study of population-based samples of nonpregnant women aged 15 to 44 years in Nigeria, Colombia, Argentina, Vietnam (2 areas), China, Thailand (2 areas), Korea, and Spain. 5,328 consenting women aged 15 to 44 years participated. Exfoliated cervical cells were collected and testing for CT and NG and human papillomavirus (HPV) was done using PCR-based assays. RESULTS: Age-standardized CT prevalence ranged between 0.2% (95% confidence interval, CI: 0.0-0.7%) in Spain and 5.6% (95% CI: 3.4-7.8%) in Nigeria. NG ranged between 0% (with broad CIs) in several areas and 2.6% (95% CI: 1.0-4.2%) in Nigeria. Prevalence of CT in all areas combined was greater in women aged 15 to 24 (4.5; 95% CI: 3.4-5.8%) than 25 to 44 (2.6; 95% CI: 2.1-3.1%), whereas NG prevalence was similar in the 2 age groups (0.3%). The only significant risk factors were NG infection (for CT), CT infection (for NG) and infection with high-risk HPV types (for both). CONCLUSIONS: The prevalence of CT and, most notably, NG was relatively low in a variety of countries. Our findings, however, do not apply to subsets of high-risk women who are likely to be underrepresented in our population-based samples.

Reproductive factors, oral contraceptive use, and human papillomavirus infection: pooled analysis of the IARC HPV prevalence surveys.

High parity, early age at first full-term pregnancy (FTP), and long-term oral contraceptive (OC) use increase cervical cancer risk, but it is unclear whether these variables are also associated with increased risk of acquisition and persistence of human papillomavirus (HPV) infection, the main cause of cervical cancer. Information on reproductive and menstrual characteristics and OC use were collected from 14 areas worldwide, among population-based, age-stratified random samples of women aged 15 years or older. HPV testing was done using PCR-based enzyme immunoassay. Unconditional logistic regression was used to estimate the odds ratios (OR) of being HPV-positive according to reproductive and menstrual factors and corresponding 95% confidence intervals (CI). When more than two groups were compared, floating CIs (FCI) were estimated. A total of 15,145 women (mean age, 40.9 years) were analyzed. Women with >or=5 FTPs (OR, 0.90; 95% FCI, 0.76-1.06) showed a similar risk of being HPV-positive compared with women with only one FTP (OR, 1.00; 95% FCI, 0.86-1.16). However, nulliparous women showed an OR of 1.40 (95% CI, 1.16-1.69) compared with parous women. Early age at first FTP was not significantly related to HPV positivity. HPV positivity was similar for women who reported >or=10 years of use of OCs (OR, 1.16; 95% FCI, 0.85-1.58) and never users of OCs (OR, 1.00; 95% FCI, 0.90-1.12). Our study suggests, therefore, that high parity, early age at first FTP, and long-term OC use are not associated with HPV prevalence, but rather these factors might be involved in the transition from HPV infection to neoplastic cervical lesions.

Historia natural de la infección por el virus del papiloma humano en una cohorte de Bogotá, D.C., Colombia / Natural history of the infection of the human papillomavirus in a cohort of Bogotá, D.C., Colombia

Objetivo: Describir la prevalencia, incidencia y persistencia de infecciones cervicales por virus del papiloma humano (VPH), C. trachomatis y sus factores de riesgo en mujeres de una cohorte en Bogotá, Colombia. Materiales y métodos: Se revisaron 6 artículos publicados de una cohorte de 1.845 mujeres bogotanas con edades entre 13 y 85 años, con citología normal y seguimiento de 5 años.Resultados: La prevalencia de infección por VPH fue 14,9por ciento. Los virus de alto riesgo fueron tres veces más comunes que los de bajo riesgo (9,0por ciento/3,2por ciento). La mayor prevalencia se observó en menores de 20 años (26 por ciento). Para tipos de bajo riesgo, la mayor prevalencia fue en mayores de 55 años (7,6por ciento). La incidencia de infección por VPH fue de 6,2 por 100 mujeres-año, 5,0 para los de alto riesgo y 2,0 para los de bajo riesgo. Siete por ciento de las infecciones prevalentes e incidentes aún estaban presentes a los 5 años de seguimiento.La eliminación de la infección por VPH16 fue más lenta que la de tipos de bajo riesgo (RR=0,47; IC95por ciento, 0,32 a 0,72) e infecciones por uno o múltiples tipos virales tuvieron tasas de eliminación similares.La prevalencia de infección por C. trachomatis fue 5,5por ciento, con un pico en mujeres menores de 20 años (8,1por ciento). Su principal factor de riesgo fueron infecciones múltiples por VPH (OR=2,8; IC95por ciento, 1,2 a 6,0). 94por ciento de las mujeres habían eliminado la infección a los 4 años de seguimiento. Las serovariantes del grupo B y el C tuvieron tasas de eliminación más lentas que el grupo intermedio (RR=0,4; IC95por ciento, 0,1 a 0,9). Conclusión: El estudio de la historia natural de la infección por VPH y C. trachomatis en un país en desarrollo contribuye significativamente al conocimiento biológico, clínico y epidemiológico de estos agentes. La prevalencia y la incidencia de VPH por tipos específicos y por edad es información necesaria para plantear nuevas estrategias de prevención del cá...

[Determining exposure history in occupational epidemiology]. / Determinación del historial de exposiciones en la epidemiolgía ocupacional.

In epidemiology, it is necessary that exposure indicators have good validity in order to obtain valid results when measuring the risks associated with occupational exposure to environmental noxious agents. However, ensuring the validity of past exposure data is no easy task. Because there are no environmental hygiene measures or representative levels of bioindicators signaling past exposure, self-reports have been used as a source of indirect exposure data. Unfortunately, data on specific agents are commonly poor and need to be complemented with data on the determinants of exposure. The validity of self-reports improves when certain techniques, such as control lists and icons, are employed, and the quality of individual exposure data improves when secondary data on exposure and its conditioning or determining factors are incorporated. Exposure can be determined by means of exposure matrices, assessment by experts, and exposure models, and by using a combination of primary and secondary data on exposure and its conditioning factors. Matrices contain pooled data and can thus lead to errors in classifying individual exposure and to biased risk estimates. Assessment by experts is probably the method with the highest validity, but it can become expensive when studies are large. It is also feasible to use a formal model for assessing perceivable exposures, complemented with expert assessments whenever the results of the model appear to deviate from reality.

Cervical coinfection with human papillomavirus (HPV) types and possible implications for the prevention of cervical cancer by HPV vaccines.

Coinfection with multiple types of human papillomavirus (HPV) and its implications for the development of efficacious HPV vaccines is a subject of great interest. To describe the occurrence of concurrent infection with multiple HPV types and to determine whether genital HPV infection modifies the risk of acquiring a new HPV infection with another HPV type, 1610 subjects were monitored for an average of 4.1 years in Bogota, Colombia. Information on risk factors for HPV infection and cervical cells was collected for detection of HPV DNA of 36 types at study entry and at 6 consecutive 6-month follow-up visits. Clustering or the concurrent acquisition of multiple types occurred more often than would be expected by chance. Subjects with incident HPV-16 or -18 infection had 5-7 times higher odds of acquiring a subsequent HPV-58 infection than subjects not infected with HPV-16 or -18. This might affect the protection conferred by effective HPV vaccines.

Determinación del historial de exposiciones en la epidemiolgía ocupacional / Determining exposure history in occupational epidemiology

La validez de los indicadores de exposición es una condición necesaria en epidemiología si se han de obtener resultados válidos en la medición de los riesgos asociados con la exposición a agentes nocivos en el entorno laboral. Sin embargo, llevar a cabo la validación de estos indicadores de exposiciones pasadas no es tarea fácil. Debido a la falta de mediciones de referencia en el ámbito de la higiene industrial y de concentraciones representativas de bioindicadores que reflejen las exposiciones pasadas, el método de los autoinformes se ha utilizado para recoger datos de exposición indirectos. No obstante, los datos acerca de agentes nocivos específicos son a menudo deficientes y deben completarse con otros sobre los factores condicionantes de la exposición. La validez de los autoinformes mejora cuando se utilizan listas de verificación e iconos ilustrativos, mientras que la calidad de la información sobre las exposiciones personales mejora cuando se incorporan datos secundarios acerca de las exposiciones y de los factores que las condicionan o determinan. La exposición se puede determinar mediante matrices de exposición, evaluación por expertos y modelos de exposición, integrando datos primarios y secundarios acerca de las exposiciones y sus factores condicionantes. Las matrices contienen datos agrupados y, por consiguiente, pueden llevar a errores a la hora de clasificar las exposiciones individuales e introducir sesgos en la estimación de los riesgos. La evaluación por expertos es probablemente el método con el índice de validez más alto, pero puede entrañar costos muy altos en el caso de estudios de cierta magnitud. Otra posibilidad con buenas perspectivas es la de utilizar un modelo formal para evaluar las exposiciones patentes y mejorarlo mediante la evaluación por expertos en situaciones en las cuales los resultados del modelo parezcan alejarse de la realidad.