viernes, 26 de febrero de 2010
Modos menos invasivos para eliminar los cálculos en los riñones y uréteres - El Hospital: Información para el desarrollo de los servicios de salud
Urología
Modos menos invasivos para eliminar los cálculos en los riñones y los uréteres
Mary K. SaMplaSKi, MD*; Brian H. Irwin, MD** y MiHir DeSai, MD***, Febrero 2010
Las intervenciones menos invasivas para la urolitiasis del tracto superior son la litotricia extracorpórea con ondas de choque, la ureteroscopia y la nefrolitotomía percutánea. Cada una tiene ventajas y desventajas, dependiendo de la localización, tamaño y composición del cálculo, y de la anatomía renal, los hábitos corporales y las comorbilidades del paciente.
No todos los cálculos requieren intervención
En los Estados Unidos, del 10 al 15% de la población desarrolla un cálculo en algún momento de su vida [1, 2], y este número está aumentando [3]. No todos ellos requieren una intervención (tabla 1).
TABLA 1. Manejo agudo del cólico renal...
En un paciente que presenta síntomas de obstrucción urinaria o sepsis, la decisión de intervenir es obvia. Los cálculos que obstruyen el flujo de la orina a menudo causan síntomas, debido a la distensión del uréter, la pelvis renal o la cápsula renal, con un patrón relativamente predecible y característico de dolor que se origina en el flanco y con frecuencia se irradia a la ingle, el testículo o los labios. Además. los cálculos de estruvita (coraliformes) no tratados, resultantes de una infección, pueden conducir a una sepsis que, en potencia, puede ser mortal.
Sin embargo, en los pacientes con cálculos asintomáticos, la decisión puede no ser clara. Cerca del 32% de quienes los tienen llegan a desarrollar síntomas en los siguientes 2,5 años, lo cual aumenta al 49% a los 5 años [3]. De los aquellos que desarrollan síntomas, la mitad requerirá un procedimiento para remover el cálculo, mientras que el resto expulsará el cálculo agresor de manera espontánea [3].
Si queda incluso un fragmento pequeño del cálculo en el riñón, después de la cirugía o de otra intervención, se puede formar de nuevo un cálculo grande, y en última instancia, deteriorar la función de esa unidad renal. Por esta razón, la mayoría de los cálculos renales deben ser tratados, o por lo menos seguidos, para detectar signos de progresión, con estudios seriados de imagenología.
En la actualidad, aunque a algunos pacientes se les da seguimiento con estudios radiológicos de riñón-uréter-vejiga, casi todos se someten a tomografía computarizada, que tiene las ventajas de delimitar con claridad la localización y el tamaño del cálculo, y establecer la presencia de cálculos ureterales pequeños y de hidronefrosis, así como su magnitud.
Si el paciente no presenta síntomas refractarios relacionados con obstrucción, y no hay signos de infección o de daño parenquimatoso, es razonable la observación con un seguimiento estricto. Sin embargo, la infección con obstrucción del tracto urinario, urosepsis, dolor o vómito intratables, lesión renal aguda, obstrucción en un riñón solitario o trasplantado, o cálculos que obstruyen bilateralmente, son todos indicaciones para una intervención urgente. Además, por su ocupación algunos pacientes que tienen cálculos asintomáticos deben ser sometidos a evaluación y tratamiento. Ejemplos de ello son los pilotos de aerolíneas y los soldados, en quienes un episodio de cólico renal intratable podría resultar peligroso.
Cálculos en mujeres
Las mujeres que están embarazadas o en edad fértil, y tienen un cálculo renal asintomático, no presentan un mayor riesgo de crecimiento del mismo y, por lo tanto, deben ser tratadas igual que cualquier otro paciente, excepto que para la obtención de imágenes se debe utilizar la ultrasonografía, con el fin de minimizar la exposición a la radiación. Debe ser enviada la orina para cultivo. Entre el 50 y el 80% de estas pacientes expulsarán sus cálculos de forma espontánea con hidratación y analgesia [4].
Se puede hacer una nefrostomía percutánea y colocación de endoprótesis ureterales (stents), si se requiere una intervención, para exponer a la paciente a la menor dosis posible de anestesia o radiación [5].
También se ha demostrado que la extracción ureteroscópica del cálculo en las pacientes embarazadas no ocasiona complicaciones relacionadas con el embarazo, e implica una mínima exposición fluoroscópica [6].
Aunque la litotricia se ha utilizado de forma inadvertida en pacientes embarazadas, su uso rutinario en estas mujeres sigue estando contraindicado [7].
Terapia médica expulsiva
Se puede intentar un manejo conservador, que consiste en hidratación oral o intravenosa y analgesia, en pacientes con cálculos renales cuya condición es por lo demás estable. De manera típica, la hidratación intravenosa se administra a una velocidad de mantenimiento [8]. La analgesia se puede suministrar tanto con medicamentos antiinflamatorios no esteroideos (AINES) como con narcóticos, aunque los AINES, en particular el ketorolaco, proporcionan el mejor control del dolor [9].
Los bloqueadores de los canales de calcio y los alfa inhiben los espasmos del uréter y promueven la expulsión espontánea de los cálculos ureterales [10]. Comparados con la hidratación sola, se ha demostrado que el nifedipino promueve un incremento absoluto del 9% en las tasas de expulsión del cálculo, y los bloqueadores alfa han producido un incremento absoluto del 29% [11]. Estos medicamentos se pueden administrar en conjunto con corticosteroides para reducir el edema ureteral, que puede contribuir a la retención del cálculo en el uréter [12].
Hasta la fecha, la terapia médica expulsiva está bien establecida únicamente para los cálculos en la parte inferior (distal) del uréter. La aplicabilidad de este tratamiento para los cálculos en el uréter proximal y en el riñón todavía está siendo investigada. En los pacientes que tienen cálculos menores de 1 cm de diámetro y cuyos síntomas están bajo control, la observación con terapia médica expulsiva puede ser apropiada. Sin embargo, después de cuatro semanas está indicada la intervención, ya que aumenta el riesgo de complicaciones y deterioro renal.
La cirugía de los cálculos se ha vuelto poco común
La mayoría de los pacientes con cálculos sintomáticos en el tracto superior eran sometidos a litotomía quirúrgica abierta antes de la aparición de la litotricia y la ureteroscopia (ver adelante). Se efectuaron muchas variantes de pielolitotomía y nefrolitotomía, incluso cirugía de banco con autotrasplante (es decir, extraer el riñón, retirar el cálculo y luego reimplantar el riñón). Sin embargo, la litotricia y la extracción ureteroscópica han reducido de manera drástica el papel de la cirugía abierta de los cálculos: en la actualidad se practica solamente en el 0,3 al 0,7% de los casos [13, 14].
La cirugía laparoscópica para los cálculos renales también se practica rara vez. Aunque casi todos los tipos de procedimientos para los cálculos se han llevado a cabo por vía laparoscópica [15-19], esta estrategia está indicada tan solo en situaciones en las que se espera que la litotricia o el tratamiento ureteroscópico fracasen.
Cálculos urinarios: elección de la intervención En la urolitiasis del tracto superior, las intervenciones menos invasivas prácticamente han reemplazado a la cirugía de litotomía clásica. La elección de la intervención depende del tamaño, el número y la localización del cálculo o los cálculos, del tipo de cálculo presente y de los factores del paciente.
Opciones menos invasivas
Litotricia para cálculos renales pequeños
La litotricia desintegra los cálculos urinarios. En este procedimiento ambulatorio no invasivo, un generador crea una onda de choque, que se propaga hacia un foco fijo centrado en el cálculo (figura 1).
Poco después de que llegó a estar disponible, la litotricia se volvió inmensamente popular, debido a su capacidad de fragmentar los cálculos sin cirugía. El tratamiento ureteroscópico ha desempeñado un papel más importante en los últimos años, por ser más versátil, pero la litotricia sigue siendo el tratamiento más común para la urolitiasis.
Ventajas, usos. En general, la litotricia está indicada para los cálculos renales menores de 2 cm [20], en especial para los que no están localizados en el cáliz, en el polo inferior. Es más efectiva para los cálculos en la pelvis renal (76% de los pacientes quedan libres de cálculos), y menos efectiva para los cálculos en el polo inferior (59% libres de cálculos) [21]. Por esta razón, de los cálculos que se encuentran en el polo inferior, solo los que miden menos de 1 cm de diámetro son tratados con litotricia.
En el pasado, la litotricia también se prefería en los pacientes que tenían cálculos en el uréter proximal, un área que técnicamente era de difícil acceso con un ureteroscopio. Los avances recientes en el diseño del ureteroscopio casi han eliminado esta dificultad.
Desventajas. La litotricia puede lesionar cualquier estructura en la trayectoria de la onda de choque, y producir sangrado, inflamación o perforación. También es posible que ocasione alteraciones en la transmisión de la señal eléctrica cardíaca, que conducen a arritmias cardíacas durante el tratamiento.
Los problemas a largo plazo incluyen un posible vínculo entre la litotricia y el desarrollo de diabetes e hipertensión [22]. La litotricia está contraindicada en el embarazo y en los estados coagulopáticos, y es menos efectiva en los pacientes con obesidad mórbida.
Es más probable que la litotricia fracase si la distancia de la piel al cálculo es mayor de 10 cm, si el polo inferior forma un ángulo agudo con el uréter o si el índice de masa corporal es superior a 30 kg/m2 (es decir, si el paciente es obeso) [23].
Nefrolitotomía percutánea para cálculos grandes o coraliformes
La nefrolitotomía percutánea es altamente efectiva para los cálculos renales, pero se asocia con más complicaciones que la litotricia o la ureteroscopia.
Consiste en introducir una aguja en el sistema colector del riñón a través de la piel y dilatar luego el tracto cerca de 1 cm. Luego se colocan los instrumentos a través de ese tracto, para desintegrar y eliminar los cálculos. En contraste con la laparoscopia, no se utiliza insuflación; el tracto percutáneo proporciona un acceso directo al riñón para la extracción del cálculo.
Ventajas, usos. Los resultados de la nefrolitotomía percutánea son uniformemente favorables a través de un amplio espectro de tamaños, composiciones y localizaciones de los cálculos. Está indicada en los pacientes que tienen cálculos renales o ureterales mayores de 2 cm, o cálculos de más de 1 cm en el polo inferior (figura 1) [24, 25].
Los cálculos coraliformes, por lo común asociados con infección, conducen a la destrucción renal, con un riesgo significativo de morbilidad e incluso de muerte si no se tratan [26]. Como estos deben ser eliminados por completo, y a menudo es difícil o imposible hacerlo con ureteroscopia o litotricia, la nefrolitotomía percutánea es el tratamiento de primera línea [24].
Desventajas. La nefrolitotomía percutánea es invasiva y conlleva los riesgos asociados de cualquier procedimiento quirúrgico mayor, como sepsis, hematoma o hemorragia perirrenal, y lesiones accidentales de los órganos adyacentes, pleura, pulmones, intestino o bazo.
La ureteroscopia ha mejorado
Con las mejoras en el diseño, el tratamiento con ureteroscopia flexible y semirrígida se ha convertido en una de las principales opciones para los cálculos urinarios, incluso para aquellos que están en el riñón (figura 1).
Ventajas, usos. La ureteroscopia ofrece un bajo riesgo de complicaciones (similar al de la litotricia), y los porcentajes libres de cálculos se aproximan a los de la nefrolitotomía percutánea para los cálculos renales de tamaño pequeño a moderado [27, 28]. Los resultados son mejores para los cálculos de menos de 1 cm, y se observan fragmentos residuales con los más grandes.
Los nuevos ureteroscopios flexibles, que se doblan hasta 270°, permiten que los cálculos en el polo inferior sean tratados en forma exitosa [29]. En conjunto con la litotricia con láser, la ureteroscopia se puede utilizar para tratar con éxito cálculos duros (densidad > 1.000 unidades Hounsfield), cálculos en pacientes obesos y cálculos refractarios a la litotricia.
Las tasas de complicaciones y segundos procedimientos son bajas, y comparada con la litotricia, la ureteroscopia toma menos tiempo para desalojar el cálculo [30]. La ureteroscopia también se puede utilizar para tratar los cálculos en riñones con anatomía compleja, en los que una mala eliminación de los fragmentos puede ser un problema [28]. Asimismo, es posible emplearla en pacientes coagulopáticos, embarazadas o con obesidad mórbida, en quienes la litotricia o la nefrolitotomía percutánea son menos efectivas o están contraindicadas.
Desventajas. Cabe destacar que la ureteroscopia es una técnica quirúrgica, y los mejores resultados los obtienen los cirujanos con más experiencia [31].
Las complicaciones de la ureteroscopia incluyen estenosis ureteral, perforación, lesión térmica, avulsión, intususcepción, infección o steinstrasse (obstrucción con fragmentos de cálculos). Además, después de la ureteroscopia con frecuencia se coloca una endoprótesis ureteral temporal, que puede causar incomodidad y requiere un procedimiento menor complementario para su extracción.
Factores que afectan la elección del tratamiento
Tamaño y localización del cálculo
Los predictores más importantes de la expulsión espontánea de los cálculos ureterales son el tamaño y la localización. En general, los cálculos pequeños tienen mayor probabilidad de ser expulsados de forma espontánea que los grandes, y los cálculos dístales tienen más posibilidades de ser expulsados que los cálculos más proximales en el tracto urinario.
Los cálculos se clasifican, en general, como ureterales (proximales, mediales o dístales) o renales (pélvicos o caliciales), dependiendo de su localización.
En el uréter. La mayoría de los cálculos ureterales menores de 5 mm de diámetro se expulsan de manera espontánea en el curso de cuatro semanas después de la aparición de los síntomas [25, 32]. En los pacientes que tienen cálculos de menos de 1 cm, cuyo dolor está controlado y que no presentan ninguna evidencia de sepsis o insuficiencia renal, un período de observación es una opción razonable [11]. Se ha demostrado que medicamentos como la tamsulosina y el nifedipino reducen la necesidad de analgesia y el tiempo de expulsión del cálculo [33, 34].
La litotricia y la ureteroscopia son las dos principales intervenciones para los cálculos ureterales.
Sin tener en cuenta el tamaño, los cálculos en el uréter por lo general pueden ser eliminados mediante ureteroscopia. Esto puede implicar una litotricia con láser o neumática dentro del uréter o la simple recuperación del cálculo intacto en la cesta ureteroscópica. La litotricia in situ es una opción para los cálculos ureterales proximales y puede ser preferida por los pacientes que desean evitar la colocación de una endoprótesis ureteral en el momento de la intervención. La nefrolitotomía percutánea se reserva para los cálculos ureterales proximales grandes (> 2 cm) o impactados, o para los casos en los que la ureteroscopia ha fracasado [35].
Para los cálculos en el uréter proximal, no se ha demostrado ninguna diferencia en las tasas de expulsión del cálculo entre la litotricia y la ureteroscopia. Para los cálculos proximales de menos de 1 cm, la litotricia tiene una tasa libre de cálculos más alta, y para los cálculos mayores de 1 cm, se ha demostrado que la ureteroscopia tiene tasas superiores libres de cálculos [11].
Para los cálculos ureterales mediales y dístales de todos los tamaños, se ha demostrado que la ureteroscopia tiene tasas superiores libres de cálculos, aunque la diferencia es estadísticamente significativa tan solo para los cálculos dístales [11].
En el riñón. Los cálculos renales grandes (> 2 cm) o coraliformes dentro del sistema colector renal se tratan mejor con nefrolitotomía percutánea, mientras que los cálculos renales menores de 1 cm, en general se pueden tratar con ureteroscopia o con litotricia.
Los cálculos dentro del sistema colector renal, que miden entre 1 y 2 cm de diámetro, se pueden tratar con ureteroscopia, litotricia, nefrolitotomía percutánea o una combinación, dependiendo de la localización y la composición del cálculo, y del deseo del paciente.
Composición del cálculo
Los cálculos de cistina y los de oxalato de calcio son duros, con una densidad superior a 1.000 unidades Hounsfield. La litotricia tiene un alto índice de fracasos con este tipo de cálculos [36].
Los cálculos de ácido úrico son más blandos y no se visualizan bien en las imágenes de rayos X. Aunque técnicamente es factible realizar una litotricia con guía ultrasonográfica, la mayoría de los profesionales prefieren utilizar la fluoroscopia para localizar el cálculo. Por esta razón, los pacientes con cálculos radiolúcidos (es decir, cálculos de ácido úrico) tampoco son buenos candidatos para la litotricia.
Los cálculos de estruvita (coraliformes), por definición, están infectados con bacterias que residen dentro del mismo cálculo. Por lo tanto, es imperativo eliminar todos los fragmentos del cálculo durante el tratamiento, para prevenir la sepsis y la reformación del cálculo. Con el tiempo, un cálculo coraliforme que no ha sido tratado conducirá a una falla de la unidad renal.
Aunque la litotricia, la ureteroscopia y la nefrolitotomía percutánea pueden utilizarse todas para tratar los cálculos coraliformes, la nefrolitotomía percutánea tiene el mejor porcentaje libre de cálculos (78%), y la litotricia tiene el más bajo (54%) [24]. Por lo tanto, se recomienda la nefrolitotomía percutánea como el primer tratamiento para estos cálculos, y cuando se utiliza la terapia combinada, debe hacerse al final la nefrolitotomía percutánea, para garantizar que el cálculo sea removido completamente [24]. Si se va a emplear la litotomía, se debe hacer por adelantado el drenaje de la unidad renal, ya sea con nefrostomía percutánea o con una endoprótesis ureteral, para garantizar que se expulsen todos los fragmentos infectados del cálculo [24].
Prevención de recurrencias
Las anomalías metabólicas que aumentan el riesgo de urolitiasis se pueden identificar y tratar hasta en 95% de los pacientes que forman cálculos recurrentes [37]. La mayoría de estos pacientes requieren modificaciones simples de la dieta, y solo un 15% tratamiento farmacológico (para obtener más información sobre este tema, ver la revisión hecha por el Dr. Phillip Hall [38]). Como la urolitiasis es común y a menudo recurrente, las intervenciones apropiadas, combinadas con la profilaxis dietética, debe minimizar la morbilidad del paciente y preservar la función renal.
Copyright © 2009, The Cleveland Clinic Foundation. Todos los derechos reservados. Este artículo se publicó originalmente en inglés en el Cleveland Clinic Journal of Medicine (Clev Clin J Med 2009;76(10):592-598). Este artículo es una traducción de inglés al español y tal traducción se deberá tener en cuenta al leerlo. Este artículo se proporciona con propósitos educativos tal como se presenta. The Cleveland Clinic Foundation (CCF) y El Hospital no garantizan la exactitud, suficiencia, integridad o disponibilidad de la información y no son responsables por errores u omisiones, o por los resultados obtenidos del uso de tal información incluida en el contenido autorizado. CCF y El Hospital no dan ninguna garantía expresa o implícita, lo que incluye, pero no se limita a, garantía de potencial comercial o capacidad para un propósito o uso particular. En ningún caso CCF o El Hospital son responsables por cualquier daño o perjuicio indirecto, especial o consiguiente en relación con el uso del contenido autorizado por parte de suscriptores u otros.
Referencias
1. Sierakowski R, Finlayson B, landes RR, Finlayson CD, Sierakowski N. The frequency of urolithiasis in hospital discharge diagnoses in the United States. Invest Urol, 1978; 15: 438-441.
2. Norlin A, Lindell B, Granberg PO, Lindvall N. Urolithiasis. A study of its frequency. Scand J Urol Nephrol, 1976; 10: 150-153.
3. Glowacki lS, Beecroft Ml, Cook RJ, Pahl D, Churchill DN. The natural history of asymptomatic urolithiasis. J Urol, 1992; 147: 319-321.
4. Denstedt JD, Razvi H. Management of urinary calculi during pregnancy. J Urol, 1992; 148: 1072-1074.
5. Swanson SK, Heilman Rl, Eversman WG. Urinary tract stones in pregnancy. Surg Clin North Am, 1995; 75: 123-142.
6. Watterson JD, Girvan AR, Beiko DT, et al. Ureteroscopy and holmium: YAG laser lithotripsy: an emerging definitive management strategy for symptomatic ureteral calculi in pregnancy. Urology, 2002; 60: 383-387.
7. Frankenschmidt A, Sommerkamp H. Shock wave lithotripsy during pregnancy: a successful clinical experiment. J Urol, 1998; 159: 501-502.
8. Springhart WP, Marquet CG, Sur Rl, et al. Forced versus minimal intravenous hydration in the management of acute renal colic: a randomized trial. J Endourol, 2006; 20: 713-716.
9. Holdgate A, Pollock T. Systematic review of the relative efficacy of nonsteroidal anti-inflammatory drugs and opioids in the treatment of acute renal colic. BMJ, 2004; 328: 1401.
10. Hollingsworth JM, Rogers MA, Kaufman SR, et al. Medical therapy to facilitate urinary stone passage: a meta-analysis. Lancet, 2006; 368: 1171-1179.
11. Preminger GM, Tiselius HG, Assimos DG, et al.; American Urological Association Education and Research, Inc.; European Association of Urology. 2007 Guideline for the management of ureteral calculi. Eur Urol, 2007; 52: 1610-1631.
12. Pearle MS, Calhoun EA, Curhan GC; Urologic Diseases of America Project. Urologic Diseases in America Project: urolithiasis. J Urol, 2005; 173: 848-857.
13. Matlaga BR, Assimos DG. Changing indications of open stone surgery. Urology, 2002; 59: 490-493.
14. Paik Ml, Wainstein MA, Spirnak JP, Hampel N, Resnick MI. Current indications for open stone surgery in the treatment of renal and ureteral calculi. J Urol, 1998; 159: 374-378.
15. Raboy A, Ferzli GS, Ioffreda R, Albert PS. Laparoscopic ureterolithotomy. Urology, 1992; 39: 223-225.
16. Winfield HN, Donovan JF, Godet AS, Clayman RV. Laparoscopic partial nephrectomy: initial case report for benign disease. J Endourol, 1993; 7: 521-526.
17. Ruckle HC, Segura JW. Laparoscopic treatment of a stone-filled, caliceal diverticulum: a definitive, minimally invasive therapeutic option. J Urol, 1994; 151: 122-124.
18. Deger S, Tuellmann M, Schoenberger B, Winkelmann B, Peters R, loening SA. Laparoscopic anatrophic nephrolithotomy. Scand J Urol Nephrol, 2004; 38: 263-265.
19. Harmon WJ, Kleer E, Segura JW. Laparoscopic pyelolithotomy for calculus removal in a pelvic kidney. J Urol, 1996; 155: 2019-2020.
20. Abdel-Khalek M, Sheir KZ, Mokhtar AA, Eraky I, Kenawy M, Bazeed M. Prediction of success rate after extracorporeal shock-wave lithotripsy of renal stones–a multivariate analysis model. Scand J Urol Nephrol, 2004; 38: 161-167.
21. Lingeman JE, Coury TA, Newman DM, et al. Comparison of results and morbidity of percutaneous nephrostolithotomy and extracorporeal shock wave lithotripsy. J Urol, 1987; 138: 485-490.
22. Krambeck AE, Gettman MT, Rohlinger AL, Lohse CM, Patterson DE, Segura JW. Diabetes mellitus and hypertension associated with shock wave lithotripsy of renal and proximal ureteral stones at 19 years of follow up. J Urol, 2006; 175: 1742-1747.
23. Pareek G, Hedican SP, Lee FT Jr, Nakada SY. Shock wave lithotripsy success determined by skin-to-stone distance on computed tomography. Urology, 2005; 66: 941-944.
24. Preminger GM, Assimos DG, Lingeman JE, Nakada SY, Pearle MS, Wolf JS Jr; AUA Nephrolithiasis Guideline Panel. Chapter 1: AUA guideline on management of staghorn calculi: diagnosis and treatment recommendations. J Urol, 2005; 173: 1991-2000.
25. Grasso M, Conlin M, Bagley D. Retrograde ureteropyeloscopic treatment of 2 cm or greater upper urinary tract and minor staghorn calculi. J Urol, 1998; 160: 346-351.
26. Blandy JP, Singh M. The case for a more aggressive approach to staghorn stones. J Urol, 1976; 115: 505-506.
27. Fabrizio MD, Behari A, Bagley DH. Ureteroscopic management of intrarenal calculi. J Urol, 1998; 159: 1139-1143.
28. Grasso M, lang G, loisides P, Bagley D, Taylor F. Endoscopic management of the symptomatic caliceal diverticular calculus. J Urol, 1995; 153: 1878-1881.
29. Grasso M. Ureteropyeloscopic treatment of ureteral and intrarenal calculi. Urol Clin North Am, 2000; 27: 623-631.
30. Peschel R, Janetschek G, Bartsch G. Extracorporeal shock wave lithotripsy versus ureteroscopy for distal ureteral calculi: a prospective randomized study. J Urol, 1999; 162: 1909-1912.
31. Anagnostou T, Tolley D. Management of ureteric stones. Eur Urol, 2004; 45: 714-721.
32. Segura JW, Preminger GM, Assimos DG, et al. Ureteral stones clinical guidelines panel summary report on the management of ureteral calculi. The American Urological Association. J Urol, 1997; 158: 1915-1921.
33. Pearle MS. Nifedipine versus tamsulosin for the management of lower ureteral stones. Int Braz J Urol, 2004; 30: 337-338.
34. Dellabella M, Milanese G, Muzzonigro G. Medical-expulsive therapy for distal ureterolithiasis: randomized prospective study on role of corticosteroids used in combination with tamsulosin-simplified treatment regimen and health-related quality of life. Urology, 2005; 66: 712-715.
35. Albala DM, Assimos DG, Clayman RV, et al. Lower pole I: a prospective randomized trial of extracorporeal shock wave lithotripsy and percutaneous nephrostolithotomy for lower pole nephrolithiasis-initial results. J Urol, 2001; 166: 2072-2080.
36. Pareek G, Armenakas NA, Fracchia JA. Hounsfield units on computerized tomography predict stone-free rates after extracorporeal shock wave lithotripsy. J Urol, 2003; 169: 1679-1681.
37. Straub M, Hautmann RE. Developments in stone prevention. Curr Opin Urol, 2005; 15: 119-126.
38. Hall PM. Kidney stones: formation, treatment, and prevention. Cleve Clin J Med, 2009; 76: 583-591.
Acerca del autor
Mary K. SaMplaSKi, MD*; Brian H. Irwin, MD** y MiHir DeSai, MD***,
*Glickman Urological and Kidney Institute, Cleveland Clinic. **Profesor Asistente de Cirugía, División de Urología, University of Vermont College of Medicine, Burlington, VT. ***Profesor de Urología, Institute of Urology, University of Southern California, Los Angeles. *El autor ha revelado que recibe honorarios por consultoría de las empresas Baxter y Hansen Medical, y posee acciones en Hansen Medical.
abrir aquí:
El Hospital: Información para el desarrollo de los servicios de salud en América Latina
jueves, 25 de febrero de 2010
DENGUE, SEROTIPO 2, EMERGENCIA EPIDEMIOLÓGICA - PARAGUAY
DENGUE, SEROTIPO 2, EMERGENCIA EPIDEMIOLÓGICA - PARAGUAY
Un comunicado de ProMED-mail
ProMED-mail es un programa de la
Sociedad Internacional de Enfermedades Infecciosas
Fecha: 23 de febrero, 2010
Fuente: Ultima Hora.com, Paraguay
[Editado por J. Torres]
El Ministerio de Salud Pública (MSP), en declaraciones del doctor Julio César Manzur, director del Servicio Nacional de Enfermedades Transmitidas por Vectores (Senepase ha confirmado en el país la circulación de tres tipos de virus de dengue (con el ingreso del serotipo 2), lo cual incrementa las probabilidades de aparición de casos de dengue grave, antes denominadas dengue hemorrágico.
Cuando una región tiene dos o más serotipos circulando al mismo tiempo, se convierte en un área hiperendémica. "El área hiperendémica está caracterizada porque hay mayor circulación de virus y entre ellos pueden aparecer cepas más virulentas. Esa es la gran amenaza para la salud pública", dijo.
De acuerdo con Manzur, se ha demostrado que a medida que aumenta el número de casos de las formas leves -es decir, a medida que la epidemia va creciendo- empiezan a aparecer también las formas severas.
"A mayor aparición de formas leves van apareciendo también más formas graves", resumió.
El director de Senepa señaló que las formas severas del dengue pueden ser causadas por cualquiera de los tres serotipos circulantes en el país (1, 2 o 3).
Hay varios factores que incluyen en la aparición de casos graves. "En primer término, la predisposición del paciente. Cada persona reacciona en forma diferente ante la agresión del virus. En segundo lugar, si la persona ya ha sido afectada por un determinado serotipo, cuando le afecta un segundo serotipo las probabilidades de desarrollar dengue grave son mayores", apuntó.
"Por eso -agregó- es que es conveniente cortar lo antes posible el brote que se pueda dar en una determinada ciudad o en un determinado departamento", señaló.
ALERTA. El pasado 1 de febrero, el Ministerio de Salud Pública declaró alerta epidemiológica ante la detección del serotipo 2 de virus del dengue (denominado DEN-2) en el país.
El hallazgo se produjo en pacientes residentes en el departamento de Amambay. La declaración de alerta señalaba que la introducción de esta nueva cepa "implica un alto riesgo para el Paraguay en caso de que se produjera una epidemia, sobre todo por el riesgo de aparición de casos graves de dengue".
La situación de alerta epidemiológica implica la puesta en marcha de los planes de contingencia departamental para la mitigación del dengue. También, la activación de los equipos regionales de respuesta rápida para la investigación exhaustiva de los brotes de síndrome febril, entre otras acciones.
ZONAS DE RIESGO. Hasta el momento, hay cinco departamentos del país con circulación activa de virus de dengue. Ellos son: Concepción (174 casos), Alto Paraná (153), Amambay (51), Central (37) y Alto Paraguay (11), además de Capital (12).
Asimismo, son también seis los departamentos que están libres de casos: San Pedro, Cordillera, Guairá, Caazapá, Itapúa y Ñeembucú.
Los casos confirmados de dengue en el país, desde el inicio del actual periodo epidémico (en noviembre de 2009), suman 477, de un total de 1.653 casos sospechosos, según el último reporte oficial. De los confirmados, 19 casos requirieron hospitalización y 9 han sido clasificados con signos de alarma. Hasta la fecha no se registró mortalidad asociada a dengue, según el MSP.
En Asunción, los barrios afectados con brotes de dengue son: Bañado Tacumbú, barrio Jara, Villa Morra, Loma Pytá, Mburucuyá, San Cristóbal y barrio Herrera.
Comunicado por: Jaime R. Torres
-- ProMED-ESP
...jt
*###########################*
ProMED-mail hace el máximo esfuerzo posible para verificar los informes que incluimos en nuestros envíos, pero no garantiza la exactitud ni integridad de la información, ni de cualquier aseveración u opinión basadas en ella. El lector debe asumir todos los riesgos incurridos al utilizar la información incluida o archivada por ProMED-mail. La Sociedad Internacional de Enfermedades Infecciosas (International Society for Infectious Diseases, ISID) y los proveedores de servicio asociados a ella no serán responsables por errores u omisiones, ni sujetos a acción legal por daños o perjuicios incurridos como resultado del uso o confianza depositados en el material comunicado o archivado por ProMED-mail.
****************************
LEISHMANIASIS VISCERAL - ISID / ARGENTINA
LEISHMANIASIS VISCERAL, MUERTE, CASOS - ARGENTINA (MISIONES)
Un comunicado de ProMED-mail
ProMED-mail es un programa de la
Sociedad Internacional de Enfermedades Infecciosas
Fecha: 24 de febrero, 2010
Fuente: Misiones Online
[Editado por J. Torres]
Un hombre de 80 años de Garupá falleció hoy miércoles a las cinco de la mañana en el sanatorio Buenos Aires de Posadas tras ser diagnosticado con un cuadro de leishmaniasis visceral.
El médico infectólogo de Salud Pública de Misiones explicó que el paciente había ingresado al centro asistencial el 19 de febrero y que no pudo ser medicado con la droga específica porque tenía antecedentes de enfermedad cardíaca y pulmonar por lo que se le suministró medicación de segunda línea para no afectar su delicado estado de salud.
El especialista agregó que se trató del primer caso mortal de la enfermedad en este año, aunque suman seis desde su detección en marzo de 2006. Desde esa fecha, además, se han confirmado 56 casos.
Por su parte, Lucía López hija de la víctima comentó en medios locales que "desde agosto del año pasado" su padre estaba bajo tratamiento médico, en principio por neumonía, y que "recién hace un mes empezó a bajar de peso", por lo cual decidió internarlo.
Comunicado por: Jaime R. Torres
-- ProMED-ESP
...jt
*############################*
ProMED-mail hace el máximo esfuerzo posible para verificar los informes que incluimos en nuestros envíos, pero no garantiza la exactitud ni integridad de la información, ni de cualquier aseveración u opinión basadas en ella. El lector debe asumir todos los riesgos incurridos al utilizar la información incluida o archivada por ProMED-mail. La Sociedad Internacional de Enfermedades Infecciosas
(International Society for Infectious Diseases, ISID) y los proveedores de servicio asociados a ella no serán responsables por errores u omisiones, ni sujetos a acción legal por daños o perjuicios incurridos como resultado del uso o confianza depositados en el material comunicado o archivado por ProMED-mail.
*****************************
What's New from the Office of Oncology Drug Products
What's New from the Office of Oncology Drug Products
http://www.fda.gov/AboutFDA/CentersOffices/CDER/ucm093885.htm
2010
FDA granted approval to rituximab (Rituxan, Genentech), in combination with fludarabine and cyclophosphamide (FC), for the treatment of previously untreated and previously treated patients with chronic lymphocytic leukemia (CLL). More Information1 (February 18, 2010)
FDA approved a risk evaluation and mitigation strategy (REMS) to ensure the safe use of Erythropoiesis-Stimulating Agents (ESAs). The medications included in the program are marketed by Amgen under the names Aranesp (darbepoetin alfa) and Epogen (epoetin alfa) and by Centocor Ortho Biotech Products under the name Procrit (epoetin alfa). FDA required Amgen, the manufacturer of these products, to develop the REMS based on studies demonstrating that use of ESAs can increase the risk of tumor growth and shorten survival in patients with cancer. More Information2 (February 16, 2010)
2009
FDA granted approval to romidepsin for injection (ISTODAX, Gloucester Pharmaceuticals Inc.) for the treatment of cutaneous T-cell lymphoma (CTCL) in patients who have received at least one prior systemic therapy. More Information3 (November 6, 2009)
FDA granted accelerated approval to ofatumumab (Arzerra, GlaxoSmithKline) for the treatment of patients with chronic lymphocytic leukemia (CLL) refractory to fludarabine and alemtuzumab. More Information4 (October 26, 2009)
FDA granted approval to pazopanib tablets (VOTRIENTTM, GlaxoSmithKline) for the treatment of patients with advanced renal cell carcinoma. More Information5 (October 19, 2009)
FDA granted accelerated approval to pralatrexate injection (FOLOTYN, Allos Therapeutics, Inc.) for the treatment of patients with relapsed or refractory peripheral T-cell lymphoma (PTCL). More Information6 (September 24, 2009)
FDA granted approval for the use of bevacizumab (Avastin, Genentech, Inc.) in combination with interferon alfa for the treatment of patients with metastatic renal cell carcinoma. More Information 7(July 31, 2009)
FDA implemented Class Labeling Changes to anti-EGFR monoclonal antibodies, cetuximab (Erbitux) and panitumumab (Vectibix): KRAS Mutations changes were made to the product labels of cetuximab (Erbitux ImClone Systems, Branchburg, NJ) and panitumumab (Vectibix Amgen, Thousand Oaks, CA). More Information8 (July 17, 2009)
FDA approved pemetrexed (Alimta) for maintenance treatment of locally advanced or metastatic nonsquamous non-small cell lung cancer patients with no disease progression after four cycles of platinum-based first-line chemotherapy. More Information9 (July 2, 2009)
FDA approves ferumoxytol (Feraheme Injection, AMAG Pharmaceuticals, Inc.) for the treatment of iron deficiency anemia in adult patients with chronic kidney disease (CKD). Ferumoxytol is an iron-containing product for intravenous (IV) administration. More Information10 (June 30, 2009)
FDA granted accelerated approval to bevacizumab injection (Avastin, Genentech, Inc.) as a single agent for patients with glioblastoma, with progressive disease following prior therapy. More Information11 (May 5, 2009)
FDA approves everolimus tablets (AFINITOR, Novartis) for treatment of patients with advanced renal cell carcinoma after failure of treatment with sunitinib or sorafenib More Information12 (March 31, 2009)
2008
FDA approved degarelix for injection (Ferring Pharmaceuticals Inc., Parsippany, NJ), a new gonadotropin releasing hormone (GnRH) receptor antagonist, for the treatment of patients with advanced prostate cancer. More Information13 (December 24, 2008)
FDA approved imatinib mesylate tablets for oral use (Gleevec, Novartis Pharmaceuticals) for the adjuvant treatment of adult patients following complete gross resection of Kit (CD117) positive Gastrointestinal Stromal Tumor (GIST). More Information14 (December 19, 2008)
FDA approved plerixafor, solution for subcutaneous injection, (Mozobil, Genzyme Corp.) for use in combination with granulocyte-colony stimulating factor (G-CSF) to mobilize hematopoietic stem cells to the peripheral blood for collection and subsequent autologous transplantation in patients with non-Hodgkin’s lymphoma (NHL) and multiple myeloma (MM). More Information 15(December 15, 2008)
FDA granted accelerated approval for eltrombopag tablets (Promacta, GlaxoSmithKline Inc.) for the treatment of thrombocytopenia in patients with chronic immune (idiopathic) thrombocytopenic purpura (ITP) More Information 16(November 20)
FDA approved bendamustine hydrochloride (TREANDA, Cephalon, Inc.), for the treatment of patients with indolent B-cell non-Hodgkin’s lymphoma (NHL) More Information 17(October 31)
FDA converted the approval of Denileukin diftitox (Ontak, Eisai Medical Research) solution for intravenous use for the treatment of persistent or recurrent CD-25 positive cutaneous T-cell lymphoma. More information 18(October 15)
FDA approves Alimta Injection for Treatment of Metastatic Non-Aquamous Non-Small Cell Lung Cancer (NSCLC).
More information19 (October 2)
FDA approves iobenguane I 123 injection for the detection of primary or metastatic pheochromocytoma or neuroblastoma.
More information20 (September 19)
FDA approves romiplostim (Nplate) for the treatment of thrombocytopenia. More information21 (August 22)
Velcade (bortezomib) is approved for initial treatment of Patients with Multiple Myeloma. More information22 (June 24)
FDA approves bendamustine hydochloride (Treanda) for the treatment of patients with chronic lymphocytic leukemia (CLL). More information23 (March 20)
Bevacizumab (Avastin) was granted accelerated approval for use in combination with paclitaxel for the treatment of patients who have not received chemotherapy for metastatic HER2 negative breast cancer. More information24 (Feb. 22)
2007
FDA approves sorafenib (Nexavar) for the treatment of unresectable hepatocellular carcinoma. More information25 (Nov. 19)
FDA grants accelerated approval of a new dosing regimen of Dasatinib (Sprycel) More information26 (Nov. 8)
FDA approves safety-related product labeling changes for the erythropoiesis-stimulating agents Epogen, Procrit, and Aranesp. (Nov. 8) More information27
FDA grants accelerated approval to nilotinib (Tasigna) to treat leukemia. More information28 (Oct. 30)
FDA approves ixabepilone for injection (Ixempra) for two indications. More information29 (Oct. 16)
FDA expands labeling for cetuximab (marketed as Erbitux). More information30 (Oct. 2)
FDA approves new uses for docetaxel (Taxotere). More information31 (Sep. 28)
FDA approves new uses for raloxifene hydrochloride (Evista). More information32 (Sept. 13)
Dexrazoxane hydrochloride (Totect) was approved for the treatment of anthracycline extravasation. More information33 (Sept. 6)
Temsirolimus (Torisel) was approved for the treatment of advanced renal cell carcinoma. More information34 (May 30)
Doxorubicin HCl liposome injection (Doxil) was approved for use in combination with bortezomib in patients with multiple myeloma. More information35 (May 17)
A new indication for dalteparin sodium injection (Fragmin) was approved. More information36 (May 1)
Eculizumab injection (Soliris) was approved for the treatment of paroxysmal nocturnal hemoglobinuria. More information37 (March 16)
Lapatinib tablets (Tykerb) was approved for advanced metastatic breast cancer patients. More information38 (March 13)
FDA approved labeling changes for erythropoiesis-stimulating agents (ESAs) epoetin alfa (marketed as Procrit, Epogen), darbepoetin alfa (marketed as Aranesp) More information39 (March 9)
FDA was notified of the results from a multicenter, double-blind, randomized, placebo-controlled study of darbepoetin alfa (Aranesp) More information40 (Feb. 22)
FDA converted approval from accelerated to regular for sunitinib malate (Sutent) for the treatment of advanced renal cell carcinoma. More information41 (Feb. 2)
abrir aquí para acceder a los vínculos:
http://www.fda.gov/AboutFDA/CentersOffices/CDER/ucm093885.htm
Rituximab by FDA
Rituximab
On February 18, 2010, the U.S. Food and Drug Administration granted approval to rituximab (Rituxan, Genentech), in combination with fludarabine and cyclophosphamide (FC), for the treatment of previously untreated and previously treated patients with chronic lymphocytic leukemia (CLL). The approval was based on a clinically meaningful and statistically significant increase in progression-free survival (PFS) observed in two randomized multicenter open-label trials in patients randomized to receive either FC or the combination of FC with rituximab (R-FC).
In both studies patients received intravenous (i.v.) fludarabine 25 mg/m2/day and cyclophosphamide 250 mg/m2/day, daily for 3 days, repeated every 28 days for a total of 6 cycles. Rituximab 375 mg/m2 by i.v. infusion was administered on day 1 of the first cycle (the day before chemotherapy) and 500 mg/m2 i.v. on day 1 of subsequent cycles (on the same day as chemotherapy). The primary efficacy outcome was PFS, defined as the time from randomization to either disease progression, relapse, or death. Secondary endpoints included overall survival (OS) and overall response rates determined by the 1996 National Cancer Institute-sponsored Working Group Guidelines.
Study ML17102, also known as CLL8, was conducted by the German CLL Study Group and enrolled treatment-naïve patients. A total of 408 patients were randomized to the R-FC arm and 409 patients to the FC arm. The median age was 61 years (30% were ≥ 65 years old), 74% were male, 31% were Binet stage C, 45% had B symptoms, and more than 99% had ECOG performance status (PS) 0-1.
The primary efficacy endpoint was PFS as determined by the investigators. The median PFS were 39.8 months and 31.5 months in the R-FC and FC arms, respectively [HR 0.56 (95% CI: 0.43, 0.71), p <0.01, log rank test]. Overall response rates were 86% (95% CI 82, 89) in the R-FC arm and 73% (95% CI 68, 77) in the FC arm.
Study BO17072, also known as REACH, conducted by Roche and Biogen Idec, enrolled 552 patients with relapsed or refractory CLL following prior systemic therapy. Patients were randomized to receive either R-FC (n=276) or FC (n=276). The median age was 62 years old (44% ≥65 years old), and 67% were male. Eighty-two percent received a prior alkylator-containing regimen and 18% received a fludarabine-containing regimen. “B” symptoms were present in 28% and 100% were ECOG PS 0-1.
The median PFS was 26.7 versus 21.7 months for the R-FC and FC arms, respectively, as determined by an independent review committee [HR 0.76 (95% CI: 0.60, 0.96), p= 0.022, log-rank test]. Overall response rates were 54% (95% CI: 48, 60) in the R-FC arm and 45% (95% CI: 37, 51) in the FC arm.
Too few events occurred at the time of regulatory submission to conduct a meaningful analysis of OS in either study. Follow-up of patients for OS is ongoing.
Across both studies, 100 patients who received R-FC and 89 patients who received FC were ≥70 years old. The results of exploratory analyses in this elderly population did not suggest a treatment benefit for the addition of Rituxan to FC in either the previously untreated [HR 1.17 (95% CI: 0.51, 2.66)] or previously treated settings [HR 1.22 (95% CI: 0.73, 2.04)].
The safety of rituximab when combined with FC was assessed in 676 patients who received the R-FC regimen. In both studies, 71% received 6 cycles and 90% received at least 3 cycles of Rituxan-based therapy. Grade 3-4 infusion reactions occurred in 7-9% of R-FC treated patients. The following Grade 3-4 adverse events were more frequently observed in the R-FC arm compared to FC arm alone: neutropenia, febrile neutropenia, leukopenia thrombocytopenia, hypotension, hepatitis B, and pancytopenia.
Rituxan is approved as a single agent for the treatment of relapsed or refractory low-grade or follicular CD-20 positive non-Hodgkin’s lymphoma (NHL) and for the treatment of patients with non-progressing low-grade CD-20 positive NHL following first-line CVP chemotherapy, or in conduction with CVP for first-line treatment of previously untreated CD20, B-cell follicular NHL and in combination with CHOP or other anthracycline-based chemotherapy regimens for the treatment of previously untreated diffuse, large B-cell CD20 positive NHL.
Serious adverse reactions of Rituxan include fatal infusion reactions, tumor lysis syndrome, severe mucocutaneous reactions, and progressive multifocal leukoencephalopathy (PML). Adverse reactions occurring in more than 25% of Rituxan-treatment patients with lymphoid malignancies are infusion reactions, fever, lymphopenia, chills, infection, and asthenia.
Full prescribing information, including clinical trial information, safety, dosing, drug-drug interactions and contraindications is available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/103705s5311lbl.pdf1
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System by completing a form online at http://www.fda.gov/medwatch/report.htm2, by faxing (1-800-FDA-0178) or mailing the postage-paid address form provided online, or by telephone (1-800-FDA-1088).
http://www.fda.gov/AboutFDA/CentersOffices/CDER/ucm201392.htm
-
SCIENCE REPORT - cedepaptv - Febrero 2010
Edición Febrero 2010
Haga click sobre http://www.cedepap.tv/sr/febrero10/ para ingresar al magazine.
Artículos:
- Haití, con el dolor en la piel
- Terapia génica para la ceguera a los colores
- Fitness para el cerebro
Entrevistados:
- Oscar A. Candia, M.D.
Modelos animales de glaucoma
- Mónica Morrow, M.D.
Criterios para Mastectomía
- Maurice Enriquez-Sarano, M.D.
Avance de las Enfermedades Valvulares
- Franz J. Wippold II, M.D.
Diagnóstico por Imágenes en Cáncer de Cerebro
- Entrevista destacada Febrero 2010
Alejandro Lepetic, M.D.
Medicina del Viajero
- Guía Práctica clínica
Esquizofrenia y el Trastorno Psicótico Incipiente
HIV/AIDS Update -Tentative approval of nevirapine tablets for oral suspension, 50 mg
On February 24, 2010, the Food and Drug Administration (FDA) granted tentative approval for nevirapine tablets for oral suspension, 50 mg, manufactured by Aurobindo Pharma Ltd.of Hyderabad, India, indicated in pediatric patients weighing at least 5 kg, in combination with other antiretrovirals for the treatment of HIV-1 infection.
Tentative approval means that FDA has concluded that a drug product has met all of the required quality, safety and efficacy standards, even though it may not yet be marketed in the U.S. due to existing patents and/or exclusivity. It does, however, make the product eligible for use under the President's Emergency Plan for AIDS Relief (PEPFAR) program outside the United States.
As with all generic applications, FDA conducts an on-site inspection of each manufacturing facility, and of the facilities performing the bioequivalence studies, to evaluate the ability of the manufacturer to produce a quality product and to assess the quality of the bioequivalence data supporting the application prior to granting approval or tentative approval to these applications.
You can find a complete list of all Approved and Tentatively Approved Antiretrovirals in Association with the President's Emergency Plan on the FDA web site.
Nevirapine is a Nonnucleoside Reverse Transcriptase Inhibitors (NNRTI).
Richard Klein
Office of Special Health Issues
Food and Drug Administration
Kimberly Struble
Division of Antiviral Drug Products
Food and Drug Administration
http://www.fda.gov/InternationalPrograms/FDABeyondOurBordersForeignOffices/AsiaandAfrica/ucm119231.htm
Medical, Statistical, and Clinical Pharmacology Reviews of Pediatric Studies
Medical, Statistical, and Clinical Pharmacology Reviews of Pediatric Studies Conducted under Section 505A and 505B of the Federal Food, Drug, and Cosmetic Act (the Act), as amended by the FDA Amendments Act of 2007 (FDAAA)
In accordance with section 505A(k)(1) of the Act (Best Pharmaceuticals for Children Act of 2007 (BPCA)) and section 505B(h)(1) of the Act (Pediatric Research Equity Act of 2007 (PREA)), as amended by FDAAA (Pub. L. No. 110-85), the following are the medical, statistical, and clinical pharmacology reviews of pediatric studies conducted in response to a Written Request issued under the BPCA and pediatric assessments conducted under PREA.
Total Number of Products Studied under BPCA = 36
Total Number of Products Studied under PREA = 47
abrir aquí para acceder al documento FDA completo (extenso y vinculante):
http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/ucm049872.htm
Announcement: Epi Info Training Courses --- May 2010
Announcement: Epi Info Training Courses --- May 2010
Weekly
February 26, 2010 / 59(07);197
Emory University's Rollins School of Public Health and CDC's National Center of Public Health Informatics will cosponsor two Epi Info training courses at Emory University in May 2010. A basic level course will be held May 17--19, and an intermediate to advanced level course will be held May 20--22. These courses are designed for practitioners of epidemiology and computing who wish to develop software applications using Epi Info for Windows.
The basic level course covers MakeView, Analysis, Enter, Epi Map, and Epi Report on a beginner's level. The intermediate to advanced level covers importing/converting other data formats; creating relational databases; advanced check-coding and using Epi Info functions; advanced analysis, including linear regression, logistic regression, Kaplan Meier, Cox proportional hazards, complex sample frequencies, tables, and means; special topics on Epi Map and Epi Report; and issues related to the enrollees' own projects.
Tuition is charged for these courses. Additional information and application forms are available from Emory University's Rollins School of Public Health by mail (attention: Pia Valeriano, 1518 Clifton Rd. NE, Rm. 746, Atlanta, GA 30322); by fax (404-727-4590); online (http://www.sph.emory.edu/epicourses); or by e-mail (pvaleri@emory.edu).
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5907a3.htm?s_cid=mm5907a3_e
Multistate Outbreak of Human Salmonella Typhimurium Infections Associated with Pet Turtle Exposure --- United States, 2008
Multistate Outbreak of Human Salmonella Typhimurium Infections Associated with Pet Turtle Exposure --- United States, 2008
Weekly
February 26, 2010 / 59(07);191-196
On September 4, 2008, the Philadelphia Department of Public Health (PDPH) and the Pennsylvania Department of Health (PADOH) notified CDC of an outbreak of possible turtle-associated human Salmonella Typhimurium infections detected by identifying strains with similar pulsed-field gel electrophoresis (PFGE) patterns in PulseNet. Turtles and other reptiles have long been recognized as sources of human Salmonella infections (1), and the sale or distribution of small turtles (those with carapace lengths <4 inches) has been prohibited in the United States since 1975 (2,3). CDC and state and local health departments conducted a multistate investigation during September--November 2008. This report summarizes the results of that investigation, which identified 135 cases in 25 states and the District of Columbia; 45% were in children aged ≤5 years. Among 70 patients with primary infection, 37% reported turtle exposure, of which 81% was to small turtles most commonly purchased from street vendors. A matched case-control study showed a significant association between illness and exposure to turtles (matched odds ratio [mOR] = 16.5). Increasing enforcement of existing local, state, and federal regulations against the sale of small turtles, increasing penalties for illegal sales, and enacting more state and local laws regulating the sale of small turtles (e.g., requiring Salmonella awareness education at the point-of-sale), could augment federal prevention efforts.
On July 9, 2008, a girl aged 2 years was brought to a Philadelphia physician's office after 3 days of diarrhea and fever. S. Typhimurium was isolated from her stool specimen. Three weeks before her illness began, the family had purchased two pet turtles with shell lengths <4 inches from a street vendor. The family reported that the child did not touch the turtles but touched the turtle aquarium. On July 28, PulseNet* was notified that stool specimens from five additional Pennsylvania patients yielded S. Typhimurium with a PFGE XbaI pattern indistinguishable from the girl's isolate (JPXX01.0416) or different by a single band (JPXX01.0006). Each of these PFGE patterns had been observed previously and comprised 1.1%--1.2% of the PulseNet Salmonella database. By mid-August, PulseNet had identified S. Typhimurium isolates matching the outbreak strain in 10 states.† Concomitantly, epidemiologic investigations led by PDPH and PADOH revealed that five of eight Philadelphia patients and two additional Pennsylvania patients reported exposure to a turtle in household settings.
Multistate Investigation
On September 4, 2008, after a turtle aquarium water sample from a Philadelphia patient's home was positive for the outbreak strain, CDC and state and local health partners initiated a multistate investigation to determine the source of infections. A case was defined as a laboratory-confirmed infection of S. Typhimurium with the outbreak strain (PFGE XbaI pattern JPXX01.0416 or JPXX01.0006) in a person with an illness onset date§ on or after March 13, 2008 (earliest reported illness onset date). A case of secondary infection (secondary case) was defined as illness in a person occurring within 2 weeks after diarrheal illness in a household or day care contact, suggesting person-to-person transmission. All cases that were not identified as secondary cases were classified as primary cases.
A total of 135 cases in 25 states and the District of Columbia were identified in the national PulseNet database (Figure 1). Among 124 patients for whom demographic information was available, median age was 7 years (range: <1--94 years), and 54 (45%) patients were aged ≤5 years; 63 (51%) were female. Reported illness onset dates ranged from March 13 to October 7 (Figure 2); 78% of illnesses occurred during June--September.
Eighty-three (61%) of 135 patients were interviewed using a more extensive questionnaire that asked about clinical symptoms, day-care attendance, reptile exposure (turtle size, species, acquisition source, and type and extent of turtle contact), and awareness of the association between reptile contact and Salmonella infection. Of the 83 patients, 35 (42%) had bloody diarrhea, and 29 (35%) were hospitalized; no deaths were reported. Twenty (24%) of 83 patients attended day care. Nine of those 20 children attended three Pennsylvania day-care centers, and they acquired secondary Salmonella infections through contact with laboratory-confirmed index cases, one in each day-care center. All the index patients acquired their infections through turtle exposure, and all 12 children were aged <2 years.
Investigators classified 70 of the 83 interviewed patients as having primary cases and 13 (16%) as secondary cases. The median age of these 70 patients was 8 years (range: <1--80 years); 43% were aged <5 years, and 36 (51%) were female. Of the 70 patients with primary cases, 26 (37%) reported exposure to turtles, and 21 reported exposures to small turtles. Among the 69% of patients who knew the source of the turtle, the majority of turtles were purchased from street vendors, flea markets, and nonpet stores (e.g., souvenir and gift shops) (Table). Seven (10%) of 70 primary patients reported other reptile exposures (e.g., snakes or iguanas). Three of six water samples from turtle habitats in patient households yielded the outbreak strain.
During September 18--October 10, 2008, a nationwide 1:1 matched case-control study was conducted to identify whether illness was associated with exposure to turtles or other reptiles. Data were collected through telephone interviews by local, state, and CDC epidemiologists using the outbreak questionnaire. For the case-control study, only primary cases with illness onset (or date of isolation of the outbreak strain, if the onset date was unknown) on or after March 13, 2008, were eligible. Controls were persons without diarrheal illness during August and were matched by case neighborhood (using reverse directory dialing) and age group (i.e., <1 year, 1--5 years, 6--17 years, ≥18 years). The questionnaire asked about history of reptile exposure for the week preceding illness onset for case-patients and during August for controls. Investigators chose August for controls to help decrease recall bias, reasoning that, without illness to delineate clearly a time period, controls might have more difficulty recalling the timing of exposures.
Thirty-seven cases and 47 controls were enrolled from 11 participating states. A total of 33 cases could not be enrolled in the case-control study because of refusal to participate, loss to follow-up, or inability to identify a matching control. Six cases had more than one matched control enrolled, and these were included in the analysis to increase study power. The median age of case-patients was 9 years (range: <1--80 years), compared with 14 years (range: <1--90 years) for controls (p = 0.44); 51% of case-patients were female, compared with 40% of controls (p = 0.34). Eighteen (49%) of 37 case-patients reported turtle exposure, compared with nine (19%) of 47 controls (mOR = 16.5) (Table). Sixteen (94%) of the 17 case-patients for whom information was available had exposure to a turtle with shell length <4 inches. Illness was not associated with exposure to nonturtle reptiles.
On October 20, 2008, PDPH issued a health advisory informing the public about the outbreak and providing recommendations for preventing illness.¶ Attempts to trace back the source of the infected turtles were unsuccessful, partly because street or flea market vendors move frequently, complicating investigation efforts. In November 2008, the Food and Drug Administration reemphasized its warning to consumers against buying small turtles.**
Reported by
C Burke, MSN, M Torres, Philadelphia Dept of Public Health; K Warren, MPH, C Sandt, PhD, Pennsylvania Dept of Health. J Adams, PulseNet Database Unit; J Webeck, DVM, G Ewald, MSPH, C Barton Behravesh, DVM, Div of Foodborne, Bacterial, and Mycotic Diseases, National Center for Zoonotic, Vector-Borne, and Enteric Diseases; A Patel, MD, Career Epidemiology Field Officer; K Neil, MD, G Han, MD, EIS Officers, CDC.
Editorial Note
This S. Typhimurium outbreak is the third multistate, turtle-associated Salmonella outbreak in the United States since 2006. Before 2006, no large multistate turtle-associated Salmonella outbreaks were identified. One reason for this apparent increase might be PulseNet, which has improved the ability to detect multistate outbreaks. Increased pet turtle ownership in the United States also might contribute to the recurrent outbreaks: the proportion of households in the United States owning pet turtles doubled during 1996--2006, from 0.5% to 1.0% (4). Together, the three recent Salmonella outbreaks account for 258 laboratory-confirmed cases of salmonellosis (5--7) and many more unreported illnesses likely occurred. As with past outbreaks, most ill persons reporting turtle exposure were exposed to turtles with shell lengths <4 inches; these turtles were mainly acquired from flea markets, street vendors, and souvenir shops. The case-control study found a significant association of Salmonella infection with turtle exposure; however, 63% of primary cases in the outbreak had no knownturtle exposure, and 60% had no reptile exposure. This might have resulted, in part, from failure to recall a turtle exposure. Parents or guardians were interviewed as proxies for young children and they might have been unaware of their child's turtle exposure outside of the home. In addition, certain patients might have had unknown indirect turtle exposure through environmental cross-contamination or unrecognized person-to-person transmission or have been sporadic or background cases.
The federal government prohibited sales of turtles with shell lengths <4 inches in 1975 (2,3), after investigations demonstrated that small turtles were a major source of human Salmonella infections, particularly in children (1). Implementation of the prohibition resulted in a substantial decline in turtle-associated human salmonellosis, preventing an estimated 100,000 Salmonella infections annually in U.S. children (8). However, because the prohibition is not fully enforced and contains exceptions (e.g., sales for bona fide scientific, educational, or exhibition purposes), turtle-associated human salmonellosis cases continue to occur. Street vendors and flea markets are a common source of illegal sales; these were common sources reported in this outbreak.
Despite recommendations from CDC to prevent turtle-associated salmonellosis in humans (Box),†† recent outbreaks suggest public education efforts have not been successful. In this outbreak, <30% of respondents knew about the association between reptiles and Salmonella; this proportion has not increased substantially compared with the 20%--29% observed in the 2007--2008 outbreak (5). Although many reptiles carry Salmonella, small turtles pose a greater risk to young children because they are perceived as safe pets, are small enough to be placed in the mouth, or otherwise can be handled inappropriately. Persons having contact with reptiles, reptile habitats (including tank water), and other surfaces contaminated with reptile feces are at risk for Salmonella infection; direct reptile contact is not necessary (9). This outbreak documents that young children without direct turtle exposure are at risk for turtle-associated salmonellosis through person-to-person transmission in child-care settings. Direct or indirect reptile contact is associated with an estimated 6% of Salmonella infections in the United States and 11% of infections among persons aged <21 years (10).
Because of the particular hazard associated with small turtles, continuing federal prohibition against sales and distribution of small turtles is needed to prevent turtle-associated salmonellosis. Few states have laws regulating small turtles, and most of these laws prohibit turtles in day-care centers or require sellers to provide educational material. Increasing enforcement of existing local, state, and federal regulations against the sale of small turtles, increasing penalties for illegal sales, and enacting more state and local laws regulating the sale of small turtles (e.g., requiring Salmonella awareness education at the point-of-sale), could augment federal prevention efforts and facilitate a more rapid public health response.
Acknowledgments
This report is based, in part, on contributions by state and local health departments; G Badolato, Philadelphia Dept of Health; A Weltman, MD, V Dato, MD, Pennsylvania Dept of Health; and K Wannemuehler, PhD, and M Sotir, PhD, Div of Foodborne, Bacterial, and Mycotic Diseases, National Center for Zoonotic, Vector-Borne, and Enteric Diseases, CDC.
References
Lamm S, Taylor A, Gangarosa E, et al. Turtle-associated salmonellosis. I. An estimation of the magnitude of the problem in the United States, 1970--1971. Am J Epidemiol 1972;95:511--7.
Food and Drug Administration. Salmonella and turtle safety. Available at http://www.fda.gov/animalveterinary/guidancecomplianceenforcement/complianceenforcement/ucm090573.htm. Accessed February 18, 2010.
Code of Federal Regulations. Turtles intrastate and interstate requirements (21 CFR 1240.62). Available at http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/cfrsearch.cfm?fr=1240.62. Accessed February 18, 2010.
American Veterinary Medical Association. U.S. pet ownership and demographics sourcebook. Schaumberg, IL: American Veterinary Medical Association; 2007.
CDC. Multistate outbreak of human Salmonella infections associated with exposure to turtles---United States, 2007--2008. MMWR 2008;57:69--72.
Harris JR, Neil KP, Behravesh CB, et al. Recent multistate outbreaks of human Salmonella infections acquired from turtles: a continuing public health challenge. Clin Infect Dis 2010;50:554--9.
CDC. Turtle-associated salmonellosis in humans---United States, 2006--2007. MMWR 2007;56:649--52.
Cohen ML, Potter M, Pollard R, Feldman RA. Turtle-associated salmonellosis in the United States: effect of public health, 1970 to 1976. JAMA 1980;243:1247--9.
Mermin J, Hoar B, Angulo FJ. Iguanas and Salmonella Marina infection in children: a reflection of the increasing incidence of reptile-associated salmonellosis in the United States. Pediatrics 1997;99:399--402.
Mermin J, Hutwagner L, Vugia D, et al. Reptiles, amphibians, and human Salmonella infection: a population-based, case-control study. Clin Infect Dis 2004;38:S253--61.
* A national molecular subtyping network for foodborne disease surveillance.
† Alabama, Illinois, New York, Ohio, Oklahoma, Pennsylvania, South Dakota, Texas, Vermont, and Virginia.
§ Date of outbreak strain isolation minus 3 days (account for the incubation period of Salmonella) was used to estimate illness onset date if that date was unknown.
¶ Available at https://hip.phila.gov/xv/portals/0/hip/health_alerts/2008/pdph-han_advisory_5_salmonellaturtleoutbreak_10202008.pdf .
** Available at http://www.fda.gov/forconsumers/consumerupdates/ucm048081.htm.
†† Also available at http://www.cdc.gov/healthypets/spotlight_an_turtles.htm.
abrir aquí para acceder al documento CDC MMWR completo del cual se reproduce un 40%:
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5907a2.htm?s_cid=mm5907a2_e
Presumptive Abortive Human Rabies --- Texas, 2009
Presumptive Abortive Human Rabies --- Texas, 2009
Weekly
February 26, 2010 / 59(07);185-190
Rabies is a serious zoonotic disease. Recovery has been well documented in only six human patients worldwide (1,2). Five of those patients had received rabies vaccinations before illness; one had not received rabies vaccination but survived infection after prolonged intensive care. In most of these survivors, moderate to profound neurologic sequelae occurred (2,3). In all six survivors, rabies was diagnosed based on exposure history, compatible clinical symptoms, and detection of rabies virus-neutralizing antibodies (VNA). This report describes the clinical course and laboratory findings of an adolescent girl with encephalitis who had not had rabies vaccination and who had been exposed to bats 2 months before illness. Antibodies to rabies virus were detected in specimens of the girl's serum and cerebrospinal fluid (CSF) by indirect fluorescent antibody test (IFA). However, the presence of rabies VNA was not detected until after she had received single doses of rabies vaccine and human rabies immune globulin (HRIG). Although the patient required multiple hospitalizations and follow-up visits for recurrent neurologic symptoms, she survived without intensive care. No alternate etiology was determined, and abortive human rabies (defined in this report as recovery from rabies without intensive care) was diagnosed. Public education should emphasize avoiding exposure to bats and other potentially rabid wildlife and seeking prompt medical attention after exposure to such animals. Rabies is preventable if rabies immune globulin and vaccine are administered soon after an exposure; however, this case also suggests the rare possibility that abortive rabies can occur in humans and might go unrecognized.
Case Report
On February 25, 2009, an adolescent girl aged 17 years went to a community hospital emergency department with severe frontal headache, photophobia, emesis, neck pain, dizziness, and paresthesia of face and forearms. The headaches had begun approximately 2 weeks before she went to the hospital (Figure). Her examination was significant for intermittent disorientation, with a Glasgow Coma Score of 14, nuchal rigidity, and fever to 102.0oF (38.9oC). Computed tomography of her head was normal. A lumbar puncture (LP) was performed and revealed a white blood cell (WBC) count of 163/mm3, no red blood cells (RBC), 97% lymphocytes, 3% monocytes, and glucose of 61 mg/dL (Table 1). The patient was treated with intravenous ceftriaxone and dexamethasone, but when CSF bacterial cultures produced no growth, these medications were discontinued. After 3 days in the hospital, the girl's symptoms resolved, and she was discharged home.
Subsequently, her headaches recurred and intensified; on March 6, she went to another local hospital with photophobia, emesis, and myalgias, particularly of the neck and back. Magnetic resonance imaging (MRI) of her head demonstrated enlarged lateral ventricles for her age; another LP was performed and revealed a protein level of 160 mg/dL, WBC count of 185/mm3, and RBC count of 1/mm3 with 95% lymphocytes and 5% macrophages (Table 1). She was transferred to a tertiary-care children's hospital that same day.
On admission to the hospital (Figure), she was afebrile, alert, and oriented. Fundoscopic examination demonstrated a blurring of disk margins bilaterally. She was photophobic with transient limitation of vision in the left visual field. Initially, she had decreased strength of the left lower and upper extremities, but it resolved during subsequent examinations. She also had a new papular pruritic rash on her arms and back. She received a diagnosis of suspected infectious encephalitis and was treated during the hospitalization with intravenous acyclovir, ceftriaxone, ethambutol, isoniazid, pyrazinadmide, and rifapmin. On March 10, the girl reported loss of sensation and strength of the right extremities, and weakness was confirmed on examination. Emesis increased, and she became agitated and combative. But these symptoms resolved the next day. Repeat LP demonstrated increased intracranial pressure (Table 1).
An extensive workup for potential etiologies of encephalitis/aseptic meningitis was performed, but no definitive etiology was determined (Table 2). On March 10, the medical team elicited a history of bat exposure, and rabies was considered in the differential diagnosis. The patient recalled that approximately 2 months before her headaches began she had entered a cave while on a camping trip in Texas and came into contact with flying bats. Although several bats hit her body, she did not notice any bites or scratches. The patient also reported owning pet ferrets and a dog; all were in good health and under routine veterinary care.
The patient reportedly had never received rabies prophylaxis. On March 11, serologic tests of serum and CSF for antirabies virus antibodies, polymerase chain reaction (PCR) tests of saliva and nuchal skin biopsy for the presence of rabies virus RNA, and direct fluorescent antibody tests of the nuchal biopsy for rabies virus antigen were performed at CDC. No rabies virus antigens or RNA were detected. However, four serum and CSF samples tested positive for rabies virus antibodies by IFA. Serum immunoglobulin G (IgG) reactivity increased to a peak dilution of 1:8192 and immunoglobulin M (IgM) to 1:32. The CSF IgG was positive up to dilution 1:32 through March 19 and by April 3 had decreased to 1:8. The CSF IgM remained negative (Table 1). The positive IFA results were corroborated by a Western blot assay performed in blinded fashion by an independent investigator. Although rabies virus can crossreact serologically with other members of the Lyssavirus genus, Kern Canyon virus (KCV) is the only other rhabdovirus associated with bats in North America that potentially could demonstrate a limited serologic crossreactivity with rabies virus. KCV RNA was not detected in the patient's skin biopsy, saliva, and CSF by nested PCR.
On March 14, after notification of positive rabies serology results, the girl received 1 dose of rabies vaccine and 1,500 IU of HRIG. Additional doses of vaccine were not administered because of concern over possible adverse effects from potentiating the immune response. On March 19 and March 29, the patient's serum tested positive for rabies VNA by the rapid fluorescent focus inhibition test (RFFIT), whereas her CSF remained negative for rabies VNA (Table 1).
The patient was managed supportively and never required intensive care. She was discharged on March 22 with clinical symptom resolution but returned to the emergency department on March 29 with recurring headache. She left before an LP could be performed, but returned to the emergency department again on April 3 with headache and emesis. At that time, an LP was performed, and her CSF opening pressure was still elevated (Table 1). After the LP, her headache resolved. She was not rehospitalized and did not return for follow up in the outpatient clinic.
Questionnaires were administered to close friends and family members of the girl and to health-care workers to assess indications for postexposure prophylaxis (PEP). Only the girl's boyfriend met the criteria and received PEP (4). The current clinical status of the patient or her boyfriend is unknown.
Reported by
G Holzmann-Pazgal, MD, A Wanger, PhD, G Degaffe, MD, C Rose, MD, G Heresi, MD, R Amaya MD, Univ of Texas School of Medicine Dept of Pediatrics; A Eshofonie, MD, H Lee-Han, PhD, A Awosika-Olumo, MD, Bur of Epidemiology, Office of Surveillance and Public Health Preparedness, Houston Dept of Health and Human Svcs, Houston, Texas. I Kuzmin, MD, PhD, CE Rupprecht, VMD, PhD, Div of Viral and Rickettsial Diseases, National Center for Zoonotic, Vector-Borne, and Enteric Diseases, CDC.
Editorial Note
This is the first reported case in which certain clinical and serologic findings indicate abortive human rabies and in which, despite an extensive medical investigation, no alternate etiology for the illness was determined. The patient's positive serologic results offer evidence of rabies virus infection; IFA and Western blot assays indicated the presence of antibodies capable of binding to rabies virus antigens before the patient received rabies PEP. Rabies virus can crossreact serologically with other members of the Lyssavirus genus, distributed in Australia, Eurasia, and Africa (5) or, theoretically, with as yet uncharacterized rhabdoviruses. However, this patient had no history of foreign travel and no evidence of infection with KCV, the only other rhabdovirus associated with bats in North America.
Laboratory diagnosis of rabies antemortem is based typically on routine detection of viral antigen in a full-thickness skin biopsy, viral RNA in the skin biopsy or saliva, or antibodies in serum and CSF. Only antibodies were found in this patient. However, viral antigen and RNA often are not detected in infected humans antemortem because of limited virus replication and intermittent viral excretion in saliva (1,4,6). Notably, the diagnosis of rabies in all human survivors has been based solely on serologic findings, including the presence of VNA, but without virus isolation or detection of viral antigens or RNA (2,6).
Certain other clinical and laboratory findings also support a diagnosis of abortive rabies in the patient described in this report. First, the onset of acute encephalopathy approximately 2 months after exposure to bats is compatible with documented incubation periods after rabies virus exposure. Second, central nervous system (CNS) findings (e.g., fever, photophobia, emesis, neck pain, dizziness, paresthesia, limitation of visual field, and altered behavior with agitation and combativeness) are compatible with clinical aspects of rabies. Although this patient did not have classic symptoms such as laryngeal spasms (manifested as hydrophobia) or autonomic instability, the lack of such symptoms has been documented in other rabies patients (1,2,6). Finally, despite an extensive medical workup, no alternate infectious etiology was identified for the patient's neurologic symptoms, increased intracranial pressure, and CSF pleocytosis.
In animal models, both cellular and humoral immune responses are important indicators in survivorship after rabies virus infection (7--9). In this report, the patient's serologic profile suggests that her immune system cleared the rabies virus before production of VNA. This might help explain the patient's atypical (i.e., waxing and waning) neurologic course. In more typical rabies cases, infected persons who have not received rabies PEP experience a rapid neurologic decline, resulting in death. Human survivors of rabies have demonstrated a vigorous immune response to the virus, as measured by serum and CSF antibody levels (2,4). However, CSF IgG in the patient in this report never exceeded a dilution of 1:32, with serum IgG reaching 1:8192, not nearly as high as values reported in previous survivors (1). Another patient, given experimental treatment, showed evidence for neurologic recovery, with high serum but low CSF VNA, but died shortly after therapy (10).
Detection of viral antibodies in serum can be indicative of previous vaccination or exposure to a lyssavirus, but does not necessarily indicate the development of disease. Contact with virus does not ultimately constitute a productive infection (e.g., the virus can be inactivated by the host innate response or by other means before replication in host cells). Similarly, a productive infection does not necessarily result in transportation of virus to the CNS. An abortive infection can occur outside the CNS, with limited replication of the virus at the exposure site and further clearance by the host immune system (7,8).
Rabies virus is a highly neurotropic pathogen, transported from the exposure site to the CNS by peripheral nerves without significant local replication and avoiding or impairing the host immune response during the incubation period. Thereafter, when the virus reaches higher concentrations in the CNS and spreads peripherally, specific antibodies can be detected as the clinical course evolves. Typically, the detection of specific virus antibodies in the CSF indicates a CNS infection. Based on evidence to date with U.S. rabies patients, antibodies to the abundant viral nucleocapsid antigens detected by IFA are registered first, whereas VNA, directed to the outer viral glycoprotein, are only detected later by RFFIT, if VNA are detected at all. The patient described in this report did not have detectable rabies VNA in the serum until after receiving rabies vaccine and HRIG.
In all previous human survivors, rabies was diagnosed based on exposure histories, compatible clinical symptoms, and detection of rabies virus antibodies. However, in all of those patients, the clinical courses were substantially longer, with more severe neurologic compromise and more prominent stimulation of the immune system, including the induction of VNA. In the case presented here, the clinical manifestation was relatively mild, which might imply variables associated with viral dose, route, and type, with a more limited virus replication and less apparent stimulation of the immune system. Clinicians treating possible cases of human rabies, indicated by acute, progressive infectious encephalitis, a compatible exposure history, and serologic evidence of a specific lyssavirus response, even in the absence of detectable VNA or fulminant neurologic decline, should contact their state health department for engagement with CDC.
Acknowledgments
This report is based, in part, on contributions by J Murphy, PhD, I Butler, MD, C Dreyer, MD, B Aalbers, MD, Univ of Texas School of Medicine; R Arafat, MD, Office of Surveillance and Public Health Preparedness, D Persse, MD, Houston Dept of Health and Human Svcs; P Grunenwald, DVM, Texas Dept of State Health Svcs, Region 6/5 South; C Kilborn, MPH, Harris County Public Health and Environmental Svcs, Houston; T Sidwa, DVM, Texas Dept of State Health Svcs, Austin, Texas; J Blanton, MPH, R Franka, DVM, PhD, M Niezgoda, MS, L Orciari, MS, A Velasco-Villa, PhD, X Wu, DVM, PhD, and P Yager, Div of Viral and Rickettsial Diseases, National Center for Emerging and Zoonotic Diseases, CDC.
References
Willoughby RE, Tieves KS, Hoffman GM, et al. Survival after treatment of rabies with induction of coma. N Engl J Med 2005;352:2508--14.
Hattwick MA, Weis TT, Stechschulte CJ, Baer GM, Gregg MB. Recovery from rabies: a case report. Ann Intern Med 1972;76:931--42.
Jackson AC, Warrell MJ, Rupprecht CE, et al. Management of rabies in humans. Clin Infect Dis 2003;36:60--3.
CDC. Human rabies prevention---United States, 2008: recommendations of the Advisory Committee on Immunization Practices. MMWR 2008;57(No. RR-3).
Calisher CH, Karabatsos N, Zeller H, et al. Antigenic relationships among rhabdoviruses from vertebrates and hematophagous arthropods. Intervirology 1989;30:241--57.
World Health Organization. WHO expert consultation on rabies: first report. WHO Technical Report Series 931. Geneva, Switzerland: World Health Organization; 2005. Available at http://www.who.int/rabies/trs931_%2006_05.pdf . Accessed February 22, 2010.
Lodmell DL, Ewalt LC. Pathogenesis of street rabies virus infections in resistant and susceptible strains of mice. J Virol 1985;55:788--95.
Bell JF. Abortive rabies infection: experimental production in white mice and general discussion. J Infect Dis 1964;114:249--57.
Perry LL, Lodmell DL. Role of CD4 and CD8 T cells in murine resistance to street rabies virus. J Virol 1991;65:3429--34.
Rubin J, David D, Willoughby RE, Jr., et al. Applying the Milwaukee Protocol to treat canine rabies in Equatorial Guinea. Scand
abrir aquí para acceder al documento CDC MMWR completo del cual se reproduce un 45%:
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5907a1.htm?s_cid=mm5907a1_e
Medicines for children
Medicines for children
Opinions and decisions on PIP applications
European Medicines Agency decisions on paediatric investigation plans (PIPs), including deferrals and waivers, and on modification of an agreed PIP
Decision types:
W – decision granting a waiver in all age groups
P – decision agreeing on a Paediatric Investigation Plan, with or without partial waiver(s) and or deferral(s)
PM – decision on the application for modification of an agreed PIP
RP – decision refers to a refusal on a proposed Paediatric Investigation Plan
RW – decision refers to a refusal on a request for request on a waiver in all age groups
Click on a column heading to sort alphabetically or by date.
abrir aquí para acceder al documento EMEA completo (extenso):
http://www.ema.europa.eu/htms/human/paediatrics/decisions.htm
Suscribirse a:
Entradas (Atom)