Increase in Salmonella enterica serovar Paratyphi A infections in Phnom Penh, Cambodia, January 2011 to August 2013.

We report an increased number of Salmonella enterica Paratyphi A infections in adults in Cambodia. Between January 2011 and August 2013, 71 S. Paratyphi A isolates were recovered from blood cultures, representing a 44-fold increase compared to July 2007 to December 2010, while monthly numbers of cultures did not change. Infections with S. Typhi increased two-fold in the same period. Most cases came from the capital Phnom Penh. These findings warrant epidemiological investigation to support public health measures.

Increase in acute malnutrition in children following the 2014-2015 Ebola outbreak in rural Sierra Leone.

Setting: All health facility and community malnutrition screening programmes in Tonkolili, a rural Ebola-affected district in Sierra Leone. Objectives: Before the Ebola disease outbreak, Sierra Leone had set a goal to reduce the prevalence of severe acute malnutrition (SAM) in children aged <5 years to <0.2%. We compared the number of children screened, diagnosed and treated for malnutrition before, during and after the outbreak (2013-2016). Design: This was a retrospective cross-sectional study. Results: Health facility screening declined from 16 805 children per month pre-outbreak to 13 510 during the outbreak (P = 0.02), and returned to pre-outbreak levels after the outbreak. Community-based screening remained stable during the outbreak, and increased by 30% post-outbreak (P < 0.001). The proportion diagnosed with moderate acute malnutrition using mid-upper arm circumference increased from respectively 3.6% and 5.1% pre-outbreak in the community and health facilities to 8.2% and 7.9% post-outbreak (P < 0.001, P = 0.003). The proportion of children diagnosed with SAM using a weight-for-age ratio at health facilities increased from 1.5% pre-outbreak to 3.5% post-outbreak (P = 0.003). On average, for every four children diagnosed with SAM per month, one child completed SAM treatment. Conclusion: After a decline in screening during the Ebola outbreak, diagnoses of acute malnutrition increased post-outbreak. Nutrition programmes need to be strengthened to pre-empt such effects in the event of future Ebola outbreaks.

Contexte : Tous les programmes de dépistage de la malnutrition par les structures de santé et dans les communautés à Tonkolili, un district rural affecté par Ebola en Sierra Leone.Objectifs : Avant la flambée épidémique d'Ebola, la Sierra Leone avait fixé l'objectif de réduire la prévalence de la malnutrition aigüe grave (MAG) chez les enfants âgés de <5 ans à < 0,2%. Nous avons comparé le nombre d'enfants dépistés, diagnostiqués et traités pour malnutrition avant, pendant et après la flambée épidémique (2013­2016).Schéma : Une étude rétrospective transversale.Résultats : Le dépistage dans les structures de santé a décliné de 16 805 enfants par mois avant Ebola à 13 510 pendant Ebola (P = 0,02), et il est revenu à son niveau d'avant la flambée dans la période post-Ebola. Le dépistage en communauté est resté stable pendant Ebola et a augmenté de 30% post-Ebola (P < 0,001). La proportion d'enfants ayant eu un diagnostic de malnutrition modérée aigüe en fonction du périmètre brachial a augmenté respectivement de 3,6% et de 5,1% avant Ebola en communauté et dans les structures de santé, de 8,2% et de 7,9% après Ebola (P < 0,001 ; P = 0,003). La proportion d'enfants ayant eu un diagnostic de MAG en fonction du poids pour l'âge dans les structures de santé est passée de 1,5% avant Ebola à 3,5% après Ebola (P = 0,003). En moyenne, un enfant a achevé son traitement de MAM sur quatre enfants ayant eu un diagnostic de MAG par mois.Conclusion : Après un déclin dans le dépistage pendant la flambée épidémique d'Ebola, les diagnostics de malnutrition aigüe ont augmenté après Ebola. Un renforcement des programmes de nutrition est nécessaire pour éviter un tel effet lors de futures flambées épidémiques.

Marco de referencia: Todos los programas institucionales y comunitarios de detección de la desnutrición en Tonkolili, un distrito rural de Sierra Leona afectado por el virus del Ébola.Objetivos: Antes del brote epidémico por el virus del Ébola, Sierra Leona se había fijado el objetivo de disminuir a <0,2% la prevalencia de desnutrición aguda grave (SAM) en los niños <5 años de edad. En el presente estudio se comparó el número de niños que participaron en la detección sistemática de la desnutrición, el número de niños diagnosticados y el de niños tratados por desnutrición antes del brote, durante el mismo y después de él (del 2013 al 2016).Método: Fue este un estudio transversal retrospectivo.Resultados: El tamizaje en los establecimientos sanitarios disminuyó de 16 805 niños por mes antes del brote a 13 510 niños por mes durante el mismo (P = 0,02) y la cifra inicial se recuperó después del brote. El tamizaje en la comunidad permaneció estable durante el brote y aumentó un 30% después del mismo (P < 0,001). Al utilizar como medida el perímetro braquial, la proporción de diagnósticos de desnutrición aguda moderada aumentó de 3,6% en la comunidad y 5,1% en los establecimientos antes del brote respectivamente a 8,2% y 7,9% después del mismo (P < 0,001, P = 0,003). Al aplicar los valores del peso para la edad en los establecimientos de salud, la proporción de niños con diagnóstico de SAM pasó del 1,5% antes del brote a 3,5% después del mismo (P = 0,003). En promedio, uno de cada cuatro niños en quienes se diagnosticó SAM cada mes completó su tratamiento.Conclusión: Después de una diminución de la detección sistemática de la desnutrición aguda grave durante el brote epidémico de enfermedad del Ébola, el diagnóstico de desnutrición aguda aumentó después del brote. Es necesario fortalecer los programas de nutrición con el fin de evitar con anticipación estas repercusiones durante los brotes epidémicos en el futuro.

Life goes on: the resilience of maternal primary care during the Ebola outbreak in rural Sierra Leone.

Setting: All 100 health facilities providing maternal services in Moyamba, Sierra Leone, a rural district that experienced a smaller Ebola outbreak than other areas. Objective: To compare trends in antenatal care (the first and fourth visit [ANC1 and ANC4]), delivery, and postnatal care (PNC1) service utilisation before, during and after the Ebola outbreak (2014-2016). Design: Cross-sectional study using secondary programme data. Results: A total of 211 Ebola cases occurred in Moyamba District. The mean number of monthly ANC visits remained stable over time, except for the subset of care provided via outreach visits where, compared with before the outbreak (n = 390), ANC1 visits declined during (n = 331, P = 0.002) and after the outbreak (n = 342, P = 0.03). Most (>97%) deliveries occurred in health facilities, assisted by maternal and child health aides (>80%). During the outbreak, the mean number of community-based deliveries per month declined from 31 to 21 (P = 0.03), and the mean number of deliveries performed by midwives increased from 49 to 78 (P < 0.001) compared with before the outbreak. Before, during and after Ebola, there was no significant change in the mean number of live births (respectively n = 1134, n = 1110, n = 1162), maternal PNC1 (respectively n = 1110, n = 1105, n = 1165) or neonatal PNC1 (respectively n = 1028, n = 1050, n = 1085). Conclusion: In a rural district less affected by Ebola transmission than other areas, utilisation of maternal primary care remained robust, despite the outbreak.

Contexte : Les 100 structures de santé offrant des services de santé maternelle à Moyamba, Sierra Leone, un district rural qui a connu une petite flambée épidémique d'Ebola.Objectif : Comparer les tendances en matière d'utilisation des services de consultation prénatale (ANC1 et ANC4, c'est-à-dire la première consultation and la quatrième consultation ANC), d'accouchement et de soins postnataux (PNC1) avant, pendant et après la flambée épidémique d'Ebola (2014­2016).Schéma : Etude transversale recourant aux données secondaires du programme.Résultats : Il y a eu 211 cas d'Ebola dans le district. Le nombre moyen mensuel des ANC est resté stable dans le temps, à l'exception du sous-ensemble de soins offert à travers des stratégies avancées où, comparé à la période précédant la flambée épidémique (n = 390), les ANC1 ont décliné pendant (n = 331 ; P = 0,002) et après Ebola (n = 342 ; P = 0,03). La majorité des activités (<97%) a eu lieu dans des structures de santé, assistées par des auxiliaires de santé maternelle et infantile (<80%). Pendant la flambée épidémique, le nombre moyen d'accouchements ayant eu lieu en communauté par mois a décliné de 31 à 21 (P = 0,03), et le nombre moyen d'accouchements réalisés par des sages-femmes est passé de 49 à 78 (P < 0,001) par comparaison à la période antérieure. Il n'y a pas eu de changement significatif avant, pendant et après Ebola, dans le nombre moyen de naissances vivantes (n = 1134, n = 1110, n = 1162), de ANC1 maternelles (n = 1110, n = 1105, n = 1165) ou de consultation néonatales (n = 1028, n = 1050, n = 1085).Conclusion : Dans un district rural moins affecté par la transmission d'Ebola, l'utilisation des soins de santé primaires maternels a résisté à la flambée épidémique.

Marco de referencia: Los 100 establecimientos de atención de salud que cuentan con servicios de maternidad en Moyamba, un distrito rural de Sierra Leona donde el brote epidémico por enfermedad del Ébola fue menos intenso.Objetivo: Comparar las tendencias de la utilización de los servicios de atención prenatal (ANC1 et ANC4, es decir, la primera y la cuarta atención ANC), parto y atención posnatal (primera cita postnatal) antes del brote de enfermedad del Ébola, durante el mismo y después de él (del 2014 al 2016).Método: Fue este un estudio transversal con datos secundarios de los programas.Resultados: Se presentaron 211 casos de enfermedad por el virus del Ébola en el distrito. El promedio de consultas mensuales de atención prenatal permaneció estable con el transcurso del tiempo, con la excepción del subconjunto de cuidados prestados por conducto de citas extrainstitucionales, donde en comparación con el periodo anterior al brote (n = 390), las citas por ANC1 disminuyeron durante el brote (n = 331; P = 0,002) y después del mismo (n = 342; P = 0,03). La mayoría de los partos (>97%) tuvo lugar en los establecimientos sanitarios, atendido por auxiliares de salud maternoinfantil (>80%). Durante el brote epidémico, el promedio mensual de partos atendidos en la comunidad disminuyó de 31 a 21 (P = 0,03) y el promedio de partos atendidos por parteras aumentó de 49 a 78 (P < 0,001) en comparación con el período anterior al brote. No se observó ningún cambio significativo antes del brote, durante el mismo o después de él, con respecto al promedio de nacidos vivos (n = 1134, n = 1110 y n = 1162), ANC1 (n = 1110, n = 1105 y n = 1165) ni de primeras consultas posnatales del recién nacido (n = 1028, n = 1050 y n = 1085).Conclusión: En un distrito rural menos afectado por la transmisión de la enfermedad del Ébola, la utilización de los servicios primarios de atención materna resistió al brote epidémico.

Ebola and community health worker services in Kenema District, Sierra Leone: please mind the gap!

Setting: All community health workers (CHWs) in rural Kenema District, Sierra Leone. Objective: CHW programmes provide basic health services to fill gaps in human health resources. We compared trends in the reporting and management of childhood malaria, diarrhoea and pneumonia by CHWs before, during and after the Ebola outbreak (2014-2016). Design: Retrospective cross-sectional study using programme data. Results: CHW reporting increased from 59% pre-outbreak to 95% during the outbreak (P < 0.001), and was sustained at 98% post-outbreak. CHWs stopped using rapid diagnostic tests for malaria mid-outbreak, and their use had not resumed post-outbreak. The average monthly number of presumptive treatments for malaria increased from 2931 pre-outbreak to 5013 during and 5331 post-outbreak (P < 0.001). The average number of monthly treatments for diarrhoea and pneumonia decreased from respectively 1063 and 511 pre-outbreak to 547 and 352 during the outbreak (P = 0.01 and P = 0.04). Post-outbreak pneumonia treatments increased (mean 1126 compared to pre-outbreak, P = 0.003), and treatments for diarrhoea returned to pre-outbreak levels (P = 0.2). Conclusion: The CHW programme demonstrated vulnerability, but also resilience, during and in the early period after the Ebola outbreak. Investment in CHWs is required to strengthen the health care system, as they can cover pre-existing gaps in facility-based health care and those created by outbreaks.

Contexte : Tous les travailleurs de santé communautaires (CHW) du district rural de Kenema, Sierra Leone.Objectif : Les programmes de CHW offrent des services de santé de base pour combler les lacunes en matière de ressources humaines en santé. Nous avons comparé les tendances du signalement et de prise en charge du paludisme, de la diarrhée et de la pneumonie de l'enfant par les CHW avant, pendant et après l'épidémie d'Ebola (2014­2016).Schéma : Étude rétrospective transversale sur les données du programme.Résultats : Les rapports des CHW ont augmenté de 59% avant l'épidémie à 95% pendant la flambée (P < 0,001), et se sont maintenus à 98% après la flambée. Les CHW ont arrêté d'utiliser les tests de diagnostic rapide pour le paludisme au milieu de l'épidémie et leur utilisation n'a pas repris après la flambée. Le nombre moyen mensuel de traitements présomptifs du paludisme a augmenté de 2931 avant la flambée à 5013 pendant et 5331 après la flambée (P < 0,001). Le nombre moyen mensuel de traitements pour diarrhée et pneumonie a diminué de 1063 et 511 avant la flambée à 547 et 352, respectivement, pendant la flambée (P = 0,01 et P = 0,04). Après la flambée, les traitements de pneumonie ont augmenté (moyenne 1126 comparée à avant la flambée, P = 0,003), tout comme les traitements pour diarrhée, qui sont remontés aux niveaux précédant la flambée (P = 0,2).Conclusion : Le programme des CHW a démontré sa vulnérabilité, mais également sa résilience, pendant la flambée et dans la brève période qui a suivi l'épidémie d'Ebola. Le renforcement du système de santé devrait investir dans les CHW car ils peuvent combler les lacunes pré-existantes des soins de santé basés dans les structures et celles créées par les épidémies.

Marco de referencia: Todos los agentes de salud comunitarios (CHW) en la zona rural del distrito de Kenema, en Sierra Leona.Objetivo: Los programas de CHWs prestan servicios básicos que compensan las deficiencias de recursos humanos del sistema de salud. En el estudio se comparó la evolución de las notificaciones y el tratamiento del paludismo, la diarrea y la neumonía en los niños por parte de los CHW, antes del brote epidémico de fiebre hemorrágica del Ébola; durante y después del mismo (2014­2016).Método: Fue este un estudio transversal retrospectivo a partir de los datos del programa.Resultado: La notificación por parte de los CHW aumentó de 59% antes del brote a 95% durante el mismo (P < 0,001) y permaneció estable en 98% después de la epidemia. Los CHW interrumpieron la utilización de las pruebas diagnósticas rápidas del paludismo en la mitad del período epidémico y no reanudaron su aplicación al finalizar el brote. El número promedio de tratamientos de presunción por paludismo aumentó de 2931 antes del brote a 5013 durante el mismo y 5331 después de la epidemia (P < 0,001). El promedio de tratamientos mensuales por diarrea y neumonía disminuyó respectivamente de 1063 y 511 antes del brote a 547 y 352 durante el mismo (P = 0,01 y P = 0,04). Después de la epidemia del Ébola los tratamientos por neumonía aumentaron (promedio 1126; P = 0,003) con respecto al período anterior al brote y los tratamientos por diarrea recuperaron las cifras anteriores a la epidemia (P = 0,2).Conclusión: Se puso de manifiesto la vulnerabilidad del programa de CHW a la epidemia del Ébola, pero se demostró también su capacidad de recuperación durante el brote y el período inicial después de la epidemia. El fortalecimiento de los sistemas de salud debe comportar una inversión en los CHW, que pueden cubrir las lagunas prexistentes de la atención institucional de la salud y las deficiencias que aparecen como resultado de las epidemias.

Influence of the 2014-2015 Ebola outbreak on the vaccination of children in a rural district of Guinea.

Setting: All health centres in Macenta District, rural Guinea. Objective: To compare stock-outs of vaccines, vaccine stock cards and the administration of various childhood vaccines across the pre-Ebola, Ebola and post-Ebola virus disease periods. Design: This was an ecological study. Results: Similar levels of stock-outs were observed for all vaccines (bacille Calmette-Guérin [BCG], pentavalent, polio, measles, yellow fever) in the pre-Ebola and Ebola periods (respectively 2760 and 2706 facility days of stock-outs), with some variation by vaccine. Post-Ebola, there was a 65-fold reduction in stock-outs compared to pre-Ebola. Overall, 24 facility-months of vaccine stock card stock-outs were observed during the pre-Ebola period, which increased to 65 facility-months of stock-outs during the Ebola outbreak period; no such stock-out occurred in the post-Ebola period. Apart from yellow fever and measles, vaccine administration declined universally during the peak outbreak period (August-November 2014). Complete cessation of vaccine administration for BCG and a prominent low for polio (86% decrease) were observed in April 2014, corresponding to vaccine stock-outs. Post-Ebola, overall vaccine administration did not recover to pre-Ebola levels, with the highest gaps seen in polio and pentavalent vaccines, which had shortages of respectively 40% and 38%. Conclusion: These findings highlight the need to sustain vaccination activities in Guinea so that they remain resilient and responsive, irrespective of disease outbreaks.

Contexte: Tous les centres de santé de la Préfecture de Macenta, en Guinée rural.Objectif: Comparer la rupture en vaccins, en cartes de stock de vaccins et l'administration des différents vaccins d'enfance pendant les périodes pré-Ebola, Ebola et post-Ebola.Schéma: Une étude écologique.Résultats: Des niveaux similaires de rupture étaient observés pour tous les vaccins (bacille Calmette-Guérin [BCG], pentavalent, polio, rougeole, fièvre jaune) dans les périodes pré-Ebola et Ebola (respectivement 2760 et 2706 jours-structure de rupture), avec quelques variations par vaccin. Post-Ebola, il y avait 65 fois plus de réduction en rupture, comparé à la période pré-Ebola. Un total de 24 mois-structure de rupture en cartes de stock de vaccins était observé pendant la période pré-Ebola, qui a augmenté à 65 mois-structure de rupture pendant la période Ebola ; une telle rupture ne s'est pas produite dans la période post-Ebola. Excepté la fièvre jaune et la rougeole, l'administration de vaccin a diminué universellement pendant la période de pointe de l'épidémie (août­novembre 2014). L'arrêt complet de l'administration de vaccin pour le BCG et une baisse marquée pour la polio (diminution de 86%) étaient observés en avril 2014, correspondant à une rupture de vaccins. Post-Ebola, l'administration globale de vaccins n'a pas atteint les niveaux pré-Ebola, avec les plus grands écarts observés aux niveaux de la polio et du pentavalent (respectivement des baisses de 40% et 38%).Conclusion: Ces résultats soulignent le besoin de maintenir les activités de vaccination en Guinée afin qu'elles restent résilientes et réactives, indépendamment de l'épidémie d'une maladie.

Marco de referencia: Todos los centros de atención de salud del distrito de Macenta en una zona rural de Guinea.Objetivo: Comparar el desabastecimiento de vacunas, las tarjetas de existencias de vacunas y la administración de las diversas vacunas de la infancia durante diferentes períodos, en función de la epidemia de fiebre hemorrágica del Ébola, a saber: antes, durante el brote y después del mismo.Método: Un estudio ecológico.Resultados: Se observaron niveles equivalentes de desabastecimientos de todas las vacunas (BCG, pentavalente, antipoliomielítica, antisarampionosa y antiamarílica) antes de la epidemia del Ébola y durante la misma (2760 y 2706 días de desabastecimiento por establecimiento, respectivamente), con alguna variación en función de las vacunas. En el período posterior a la epidemia se presentó una tasa de desabastecimientos 65 veces menor, en comparación con el período anterior a la epidemia. En general, se observaron 24 meses-centro de desabastecimiento en las tarjetas de existencias vacunales durante el período pre-Ébola, que aumentaron a 65 meses-centro de desabastecimiento durante la epidemia; en el período posterior al brote no ocurrió este tipo de desabastecimiento. Con la excepción de la vacuna antiamarílica y la antisarampionosa, la administración de vacunas disminuyó globalmente durante el período de máxima actividad de la epidemia (de agosto a noviembre del 2014). Se observó una interrupción total de la administración de BCG y una tasa considerablemente baja de administración de vacuna antipoliomielítica (disminución de un 86%) en abril del 2014, que correspondió con el desabastecimiento de vacunas. Después de la epidemia del Ébola, la administración general de vacunas no recuperó el nivel anterior al brote y las mayores carencias se observaron con la vacuna antipoliomielítica y la pentavalente (40% y 38% de déficit, respectivamente).Conclusión: Los resultados del presente estudio destacan la necesidad de sostener las actividades de vacunación en Guinea, de manera que conserven su capacidad de recuperación y de respuesta, con independencia de los brotes epidémicos.

High mortality in tuberculosis patients despite HIV interventions in Swaziland.

SETTING: All health facilities providing tuberculosis (TB) care in Swaziland. OBJECTIVE: To describe the impact of human immunodeficiency virus (HIV) interventions on the trend of TB treatment outcomes during 2010-2013 in Swaziland; and to describe the evolution in TB case notification, the uptake of HIV testing, antiretroviral therapy (ART) and cotrimoxazole preventive therapy (CPT), and the proportion of TB-HIV co-infected patients with adverse treatment outcomes, including mortality, loss to follow-up and treatment failure. DESIGN: A retrospective descriptive study using aggregated national TB programme data. RESULTS: Between 2010 and 2013, TB case notifications in Swaziland decreased by 40%, HIV testing increased from 86% to 96%, CPT uptake increased from 93% to 99% and ART uptake among TB patients increased from 35% to 75%. The TB-HIV co-infection rate remained around 70% and the proportion of TB-HIV cases with adverse outcomes decreased from 36% to 30%. Mortality remained high, at 14-16%, over the study period, and anti-tuberculosis treatment failure rates were stable over time (<5%). CONCLUSION: Despite high CPT and ART uptake in TB-HIV patients, mortality remained high. Further studies are required to better define high-risk patient groups, understand the reasons for death and design appropriate interventions.

Contexte : Toutes les structures de santé offrant une prise en charge de la tuberculose (TB) au Swaziland.Objectif : Décrire l'impact des interventions pour le virus de l'immunodéficience humaine (VIH) sur les tendances des résultats du traitement de la TB en 2010­2013, au Swaziland. Décrire l'évolution de la notification des cas de TB, la couverture du test VIH, de le traitement antirétroviral (TAR) et du traitement préventif au cotrimoxazole (CPT) et la proportion de patients coinfectées par TB-VIH avec les mauvais résultats du traitement incluant la mortalité, les abandons et les échecs du traitement.Schéma : Etude descriptive rétrospective basée sur les données agrégées du programme national TB.Résultats : Entre 2010 et 2013, les notifications de cas de TB auSwaziland ont diminué de 40%, le test VIH a augmenté de 86% à 96%, la couverture du CPT a augmenté de 93% à 99% et la couverture du TAR parmi les patients tuberculeux est passée de 35% à 75%. Le taux de coinfection TB-VIH est resté autour de 70% et la proportion de cas de TB-VIH avec des résultats médiocres a diminué de 36% à 30% entre 2010 et 2013. La mortalité est restée élevée entre 14% et 16% pendant la période d'étude et les taux d'échec du traitement TB ont été stables dans le temps (<5%).Conclusion : En dépit d'une couverture élevée du CPT et du TAR parmi les patients TB-VIH, la mortalité est restée élevée. D'autres études sont nécessaires pour mieux définir les groupes de patients à haut risque, pour mieux comprendre les causes de décès et pour concevoir des interventions appropriées.

Marco de referencia: Todos los establecimientos de salud que prestan atención antituberculosa en Swasilandia.Objetivo: Describir la repercusión de las intervenciones contra el virus de la inmunodeficiencia humana (VIH) sobre la evolución de los desenlaces terapéuticos de la tuberculosis (TB) del 2010 al 2013 en Swasilandia. Describir la evolución de la notificación de casos de TB, la aceptación de la prueba diagnóstica del VIH, el tratamiento antirretrovírico (TAR) y del tratamiento preventivo con cotrimoxazol (CPT) y la proporción de pacientes coinfectados por el VIH y el bacilo de la TB que presenta desenlaces terapéuticos desfavorables como la mortalidad, la pérdida durante el seguimiento y el fracaso del tratamiento.Método: Fue este un estudio descriptivo retrospectivo a partir de los datos agregados del Programa Nacional contra la TB.Resultados: Del 2010 al 2013, la notificación de casos de TB en Swasilandia disminuyó un 40%, la aceptación de la prueba diagnóstica del VIH aumentó de 86% a 96%, la utilización del CPT aumentó del 93% al 99% y en los pacientes con TB, y la aceptación del TAR aumentó del 35% al 75%. La tasa de coinfección permaneció alrededor del 70% y la proporción de estos pacientes que presentaba desenlaces desfavorables disminuyó del 36% en el 2010 al 30% en el 2013. Durante el período del estudio la mortalidad permaneció alta, entre el 14% y 16%, y las tasas de fracaso del tratamiento antituberculoso permanecieron estables con el transcurso del tiempo (menos del 5%).Conclusión: Pese a una alta aceptación del CPT y el TAR por parte de los pacientes coinfectados por el VIH y la TB, la mortalidad sigue siendo alta. Se precisan nuevos estudios que definan con mayor precisión los grupos de pacientes con alto riesgo de desenlaces desfavorables y que contribuyan a comprender las causas de las defunciones y a diseñar intervenciones apropiadas.

Effects of increased liver blood flow on the kinetics and dynamics of recombinant tissue-type plasminogen activator.

OBJECTIVE: To investigate the influence of increased liver blood flow on the pharmacokinetics and pharmacodynamics of recombinant tissue-type plasminogen activator (rt-PA) and to study the changes in endogenous urokinase-type plasminogen activator (u-PA). METHODS: This open, randomized, crossover trial was carried out in a clinical research unit. Eight healthy, nonsmoking volunteers received linear infusions of 24 mg rt-PA and 92 mg indocyanine green over 160 minutes. Sixty minutes after the infusions were started, the subjects consumed a standardized meal to increase liver blood flow on one occasion and abstained from taking food on the other occasion. Plasma concentrations of indocyanine green, tissue-type plasminogen activator (t-PA) antigen, t-PA activity, total u-PA antigen, plasmin-activatable single-chain u-PA (scu-PA), active two-chain u-PA (tcu-PA), fibrinogen, total fibrin, and fibrinogen/fibrin degradation products (TDP), and alpha 2-antiplasmin were measured. RESULTS: After the consumption of the meal, the area under the curve (AUC) was 35% (95% confidence interval [CI]: 25%, 43%) lower for indocyanine green, 15% (CI: 6%, 24%) lower for t-PA antigen, and 11% (CI: 2%, 19%) lower for t-PA activity compared to the AUC after subjects abstained from food. No changes were observed in fibrinogen, TDP, or alpha 2-antiplasmin concentrations that were attributable to the intake of food. The infusion of rt-PA caused a fivefold increase in the concentration of active tcu-PA and a concomitant decrease in scu-PA concentrations by more than 50%. CONCLUSIONS: Increased liver blood flow results in an increase in t-PA clearance. The conversion of the inactive zymogen scu-PA to the active tcu-PA is increased by an infusion of rt-PA, but total u-PA antigen concentrations remain unchanged.

Tolrestat pharmacokinetic and pharmacodynamic effects on red blood cell sorbitol levels in normal volunteers and in patients with insulin-dependent diabetes.

OBJECTIVES: To examine the effect of diabetes mellitus on the pharmacokinetics of tolrestat and to investigate its effect on red blood cell sorbitol levels according to a new pharmacodynamic model for this class of drugs. METHODS: Single and multiple doses of tolrestat (200 mg/twice a day) were administered to 12 patients with insulin-dependent (type I) diabetes and 12 healthy volunteers in an open parallel trial. RESULTS: Tolrestat disposition was characterized by first-order absorption and biexponential disposition: In normal subjects the terminal disposition half-life (t1/2) was 13 +/- 3 hours (mean +/- SD) and the apparent oral clearance (CL/F) was 48 +/- 9 ml/hr/kg, similar to the values in patients with type I diabetes mellitus (t1/2 = 14 +/- 4 hours; CL/F = 55 +/- 10 ml/hr/kg). Red blood cell sorbitol concentrations, which declined because of tolrestat's inhibition of aldose reductase, were characterized by an indirect-response model including a 50% inhibition constant (IC50) for production of sorbitol by aldose reductase. The removal of sorbitol (kout) was slower in patients with diabetes. The plasma IC50 averaged 2.0 +/- 1.3 micrograms/ml in normal subjects and 2.5 +/- 1.9 micrograms/ml in patients with diabetes. IC50 values expressed in free (unbound) concentrations (fu = 0.64%), which ranged from 12 to 16 ng/ml, were similar to the in vitro IC50 for inhibition of sorbitol accumulation in human red blood cells. CONCLUSIONS: Tolrestat pharmacokinetics were similar in normal subjects and in patients with diabetes; however, the patients with diabetes had higher baseline sorbitol levels (11 versus 5 nmol/ml for normal subjects) and slower sorbitol efflux rates. The proposed biochemically realistic, dynamic model characterized well the red blood cell sorbitol response patterns after administration of single and multiple doses of tolrestat.

Effects of liver blood flow on the pharmacokinetics of tissue-type plasminogen activator (alteplase) during thrombolysis in patients with acute myocardial infarction.

BACKGROUND: The removal of recombinant tissue-type plasminogen activator (rt-PA; alteplase) by the liver is so rapid that liver blood flow becomes rate determining for its clearance. In patients with myocardial infarction changes in liver blood flow may result from impaired cardiac performance or drug treatment. OBJECTIVE: To estimate the effect of variations in liver blood flow on t-PA plasma concentrations during thrombolytic therapy. METHODS: Fifteen patients with acute myocardial infarction were investigated in an open single-center study at the coronary care unit of University Hospital Leiden. Patients received thrombolytic treatment with 100 mg rt-PA over 3 hours. Liver blood flow was estimated by indocyanine green clearance and by Doppler echocardiography. Concentrations of t-PA antigen, t-PA activity, indocyanine green, alpha 2-antiplasmin, fibrinogen, and fibrin and fibrinogen degradation products were measured. RESULTS: Indocyanine green clearance and clearance of both t-PA antigen (r = 0.78; p < 0:01) and t-PA activity (r = 0.54; p < 0.05) were significantly related. Significant associations between t-PA antigen and fibrin and fibrinogen degradation products and between t-PA antigen and alpha 2-antiplasmin were also found. CONCLUSIONS: The liver blood flow of patients with myocardial infarction is inversely correlated with plasma concentrations of t-PA. In patients with severely impaired liver blood flow and heart failure, high t-PA plasma concentrations may occur if standard doses are given. This finding could contribute to optimization of the dosage of t-PA in certain patient groups.

Effects of changing liver blood flow by exercise and food on kinetics and dynamics of saruplase.

OBJECTIVE: To investigate the influence of changes in liver blood flow on the pharmacokinetics and pharmacodynamics of single-chain unglycosylated urokinase-type plasminogen activator. METHODS: This open, randomized, crossover trial was carried out in the clinical research unit. Infusions of 37.5 mg saruplase and 90 mg indocyanine green were administered over 150 minutes to 10 healthy male volunteers. After 60 minutes the subjects consumed a standardized meal to increase liver blood flow or performed an exercise test (20 minutes) to decrease liver blood flow. Indocyanine green concentrations, total urokinase-type plasminogen activator (u-PA) antigen, two-chain u-PA activity, fibrinogen, total degradation products, alpha 2-antiplasmin, and factor XII-dependent fibrinolytic activity were measured. Blood flow was measured after food intake in a portal vein branch with Doppler echography. RESULTS: The weighted average indocyanine green concentration after exercise was increased by 29% compared with baseline (steady-state concentration) values (95% confidence intervals [CI]: +6%, +56%). After food, the concentration was 27% lower compared with baseline values (95% CI: -35%, -19%), and portal vein flow was increased by a maximum of 103% (95% CI: +71%, +136%). Average maximal concentrations of u-PA antigen after exercise were increased by 130 ng/ml compared with baseline concentrations (95% CI: +65, +195 ng/ml) and, unexpectedly, 156 ng/ml higher after food (95% CI: +59, +253 ng/ml). Although not significant, an increase in average u-PA antigen concentration compared with baseline values was detected after both exercise (7%) and food (13%). This tendency toward a larger effect after food compared with the effect after exercise was reflected by minor changes in the pharmacodynamics. CONCLUSIONS: u-PA plasma concentrations were increased by reduced liver blood flow induced by exercise. Food intake produced an unexpected increase in u-PA concentrations despite increases in liver blood flow.

On the role of C1-inhibitor as inhibitor of tissue-type plasminogen activator in human plasma.

An enzyme immuno assay was developed to measure complexes of tissue-type plasminogen activator (t-PA) with C1-inhibitor in order to study the role of C1-inhibitor as an inhibitor of t-PA in plasma. In vitro experiments with melanoma and recombinant t-PA learned that purified C1-inhibitor reacts with both single chain t-PA and two chain t-PA. The rate constants ranged from 3.0 to 5.2 M-1s-1. In plasma, melanoma and recombinant two chain t-PA were hardly inhibited by C1-inhibitor, in contrast to melanoma and recombinant single chain t-PA which were inhibited to the same extent by endogenous C1-inhibitor as they were by purified C1-inhibitor. In vivo, t-PA/C1-inhibitor complex could be measured in plasma in a few cases in healthy volunteers (0.62 +/- 0.43 ng/ml t-PA equivalents), after exercise (0.84 +/- 0.25 ng/ml t-PA equivalents) and after a desmopression infusion (0.26 +/- 0.04 ng/ml t-PA equivalents). However, t-PA/C1-inhibitor complex was found in plasma in all cases after venous occlusion (1.7 +/- 0.5 ng/ml t-PA equivalents), in peritoneal fluid from patients suffering from peritoneal inflammatory disease (2.2 +/- 1.3 ng/ml t-PA equivalents) and in plasma from healthy volunteers during a t-PA infusion (27.7 +/- 18.5 ng/ml t-PA equivalents at peak level). In the last case, about 8% of the infused dose of recombinant t-PA (alteplase) was inhibited by C1-inhibitor at peak level.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of changes in liver blood flow on the pharmacokinetics of saruplase in patients with acute myocardial infarction.

BACKGROUND: The recombinant unglycosylated single chain urokinase-type plasminogen activator saruplase is cleared for a large part by the liver. A large interindividual variation in saruplase concentration is found in acute myocardial infarction (AMI) patients. The variable cardiac performance after an infarct may induce differences in liver blood flow that could explain the concentration diversity. This study was performed to investigate the relation between hepatic blood flow and the pharmacokinetic and pharmacodynamic properties of saruplase. METHODS AND RESULTS: Thirteen AMI patients were enrolled in this open label study. Patients received a bolus injection of 20 mg saruplase followed by a one-hour infusion of 60 mg saruplase. Concurrently 36 mg intravenous indocyanine green (ICG) was given over 1 h to measure hepatic blood flow. Blood samples were taken at regular time intervals to measure plasma levels of urokinase-type plasminogen activator (u-PA) antigen and activity, the two-chain form (tcu-PA) activity, indocyanine green, fibrinogen, fibrin and fibrin degradation products, alpha2-antiplasmin and thrombin antithrombin III complex. A correlation was seen between the clearance of ICG and both those of u-PA antigen (r = 0.62; p <0.05) and u-PA activity (r = 0.57; p <0.05). A negative correlation was seen between the area under the curve of tcu-PA activity and the areas under the effect curves of both fibrinogen and alpha2-antiplasmin (r = -0.84; p <0.01 and r = -0.65; p <0.05). CONCLUSIONS: Liver blood flow is an important determinant of the clearance of u-PA antigen and activity and reduction of flow in patients with heart failure will lead to an increase in plasma concentrations. High plasma concentrations of tcu-PA activity lead to increased systemic fibrinogenolysis. These results may be used to optimize saruplase treatment in patients with impaired cardiac function or after co-medication with drugs that affect liver blood flow.

Effect of isotretinoin on endogenous tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor 1 (PAI-1) in humans.

The effect of isotretinoin on fibrinolysis was investigated in 10 healthy, male volunteers in a randomized, double-blind, crossover-designed study. Isotretinoin (40 mg) was administered in the morning and in the evening for 5 days. t-PA, u-PA and PAI-1 antigen and activity in plasma were measured every morning at 9 a.m. on days 1 to 4 and every 3 hours over 24 hours on day 5. Isotretinoin treatment had no significant stimulatory effect on endogenous t-PA antigen and activity in morning plasma samples nor on their circadian variation. Also, u-PA antigen levels did not change after isotretinoin treatment. Mean PAI-1 antigen and PAI activity in 9 a.m. plasma samples were non-significantly higher during isotretinoin than during placebo treatment. After treatment with isotretinoin a significant rise of fasting triglyceride plasma levels was observed as compared to placebo. The study shows that isotretinoin has no clinically significant effect on endogenous fibrinolysis.

Drug interactions with thrombolytic agents. Current perspectives.

Thrombolytic agents are widely used for the treatment of acute thromboembolic diseases, especially acute myocardial infarction (AMI). These compounds include streptokinase, anistreplase, alteplase, urokinase and, although not commercially available yet, saruplase (prourokinase). The therapeutic window of these compounds is relatively small and subtherapeutic or toxic plasma concentrations may have serious clinical implications (insufficient thrombolysis, reocclusion and bleeding). Among the factors that affect the pharmacokinetics and pharmacodynamics of thrombolytic agents, comedication is especially relevant since these drug interactions are partly predictable and sometimes preventable. Based on knowledge of the pharmacology of thrombolytic agents and general mechanisms by which pharmacokinetic drug interactions occur, interactions with alteplase and saruplase are expected. The clearance of alteplase is dependent on hepatic blood flow (HBF), and scientific evidence is emerging that saruplase is also a high-clearance compound. Each pharmacological agent that alters HBF and is given concurrently with one of these agents can change the plasma concentrations of those thrombolytics. Although there are no published data confirming drug-induced changes in the metabolism of alteplase or saruplase by this mechanism in humans, indirect supportive evidence (clinical observations and animal experiments) is available. An overview is presented of the anticipated effects of compounds that are frequently coadministered with thrombolytic agents on the pharmacokinetics of the thrombolytics with high-clearance properties. Since the clearance of these thrombolytics may be strongly affected by hypoperfusion of the liver as a result of cardiogenic haemodynamic failure, the role of circulatory changes in potential drug-drug interactions is also discussed. Pharmacodynamic drug interactions are highly relevant in the treatment of acute thrombotic lesions and are still being evaluated to further optimise treatment strategies. As most of these treatments exist as combinations of thrombolytic, antithrombin and antiplatelet compounds, beneficial effects are partly offset by bleeding complications. Changes in the pharmacokinetics and/or pharmacodynamics of thrombolytic agents may have serious consequences. It becomes imperative for the practising physician to be aware of benefits and risks of interactions with thrombolytic agents and especially of the fact that the principal way by which the pharmacokinetics of alteplase and, presumably, saruplase can be affected is by drug- and/or haemodynamic failure-induced changes of HBF.

The effect of m-CPP on tics and obsessive-compulsive phenomena in Gilles de la Tourette syndrome.

RATIONALE: Family genetic and phenomenological studies support an interrelationship between Gilles de la Tourette syndrome (GTS) and obsessive-compulsive disorder (OCD). Some authors consider GTS as part of a serotonergically mediated cluster of OCD spectrum disorders. OBJECTIVE: To study serotonergic mechanisms in GTS, the effect of the relatively selective 5-HT2c agonist meta-chlorophenylpiperazine (m-CPP) was assessed. METHODS: We studied the behavioural effects of m-CPP on tics, obsessions, compulsions and impulsions of GTS. Twelve medication-free GTS patients (ten men, two women) were included in a single dose 0.5 mg/kg oral m-CPP challenge study with a double-blinded placebo-controlled cross-over design. Global symptom scores, target symptom scores as well as biochemical measures were followed up to 24 h after baseline. RESULTS: While m-CPP caused a significant rise in plasma cortisol and prolactin levels, no significant effects were found on the tics, obsessions and compulsions. Impulsions showed a trend to ameliorate. CONCLUSIONS: This study does not support a predominant role for 5-HT on the tics in GTS. The trend of impulsions to ameliorate after m-CPP can be interpreted as circumstantial support for impulsivity-related 5-HT hypofunctionality in GTS. However, the large variability of m-CPP plasma concentrations found in this study casts doubts upon the reliability of m-CPP as a probe for challenge studies.

Leishmaniasis in immunosuppressed individuals.

Leishmaniasis is a vector-born chronic infectious disease caused by a group of protozoan parasites of the genus Leishmania. Whereas most immunocompetent individuals will not develop disease after Leishmania infection, immunosuppression is a well-established risk factor for disease. The most severe form is visceral leishmaniasis (VL), which is typically fatal if untreated. Whereas human immunodeficiency virus (HIV) co-infection (VL-HIV) was initially mainly reported from southern Europe, it is now emerging in other regions, including East Africa, India, and Brazil. VL has also been found in a wide range of non-HIV-related immunosuppressive states, mainly falling under the realm of transplantation medicine, rheumatology, haematology, and oncology. Clinical presentation can be atypical in immunosuppressed individuals, being easily misdiagnosed or mistaken as a flare-up of the underlying disease. The best diagnostic approach is the combination of parasitological and serological or molecular methods. Liposomal amphotericin B is the drug of choice. Treatment failure and relapse rates are particularly high in cases of HIV co-infection, despite initiation of antiretroviral treatment. Primary prophylaxis is not recommended, but secondary prophylaxis is recommended when the patient is immunosuppressed. Cutaneous leishmaniasis can have a number of particular features in individuals with immunosuppression, especially if severe, including parasite dissemination, clinical polymorphism with atypical and often more severe clinical forms, and even visceralization. Mucosal leishmaniasis is more common. Treatment of cutaneous and mucosal leishmaniasis can be challenging, and systemic treatment is more often indicated. With globally increased travel and access to advanced medical care in developing countries, the leishmaniasis burden in immunosuppressed individuals will probably continue to rise, warranting increased awareness and enhanced surveillance systems.

Constraints in the diagnosis and treatment of Lassa Fever and the effect on mortality in hospitalized children and women with obstetric conditions in a rural district hospital in Sierra Leone.

BACKGROUND: Lassa fever (LF) is an acute viral haemorrhagic infection, endemic in West Africa. Confirmatory diagnosis and treatment (ribavirin) is difficult, expensive, and restricted to specialised hospitals. Among confirmed and suspected LF cases, we report on clinical and laboratory features, timing and administration of ribavirin and the relationship with case fatality. METHODS: We conducted an audit of patient files of suspected LF cases admitted to a pediatric and obstetric referral hospital in rural Sierra Leone (April 2011 to February 2012). RESULTS: There were 84 suspected LF cases; 36 (43%) were laboratory-confirmed cases, of whom only 20 (56%) received ribavirin after a median duration of eight days (IQR 314 days) of hospital admission. Of 16 patients who did not receive ribavirin, 14 (87%) died before ribavirin treatment could be commenced. Starting ribavirin within six days of admission was associated with a case fatality of 29% (2/7), while starting ribavirin later than six days was associated with a case fatality of 50% (6/12). Among the 48 suspected LF cases without laboratory confirmation, there were 21 (44%) deaths. CONCLUSIONS: These findings highlight shortcomings in LF management, including diagnostic and treatment delays. More research and development efforts should be devoted to this 'neglected disease'.

How well are asthma treatment cards filled out in public health centres in Gazeera State, Sudan?

SETTING: Four public district hospitals offering asthma treatment in Gazeera State, Sudan. Incomplete recording of patient data directly affects the quality of asthma care and the evaluation of asthma management programmes. OBJECTIVE: To assess the completeness of filling out of treatment cards and accuracy of calculating peak expiratory flow (PEF) for confirming diagnosis and grading severity of asthma. DESIGN: Cross-sectional audit of asthma treatment cards from asthma centres, 2006-2012. RESULTS: Of 959 patient cards assessed, completeness ranged from 47% to 98%. Six of 13 variables had an unsatisfactory grade of completeness (<80% complete). Calculated PEF was indicated in 885 (92%) cards, but was correct in only 609 (69%). PEF variability was recorded in 835 (87%) cards, but was correctly calculated in 442 (53%). A scheduled follow-up visit was attended by only 359 (37%) patients, indicating 63% loss to follow-up. Contact telephone numbers were missing from 453 (47%) cards. CONCLUSION: This is the first study in Africa to assess the data completeness and integrity of asthma patient cards, identifying important shortcomings. This affects quality of management of asthma patients and programme evaluation. Steps to rectify this situation are urgently needed.

Contexte : Quatre hôpitaux publics de district offrant un traitement de l'asthme dans l'état de Gazeera, Soudan. La saisie incomplète des données relatives aux patients affecte directement la qualité des soins de l'asthme et l'évaluation des programmes de prise en charge.Objectif : Evaluer l'exhaustivité du remplissage des cartes de traitement et l'exactitude des calculs de débit expiratoire de pointe (DEP) pour la confirmation du diagnostic et l'estimation du degré de gravité de l'asthme.Schéma : Audit transversal des cartes de traitement de patients asthmatiques dans les centres de prise en charge, de 2006 à 2012.Résultats : Sur 959 cartes de patients évaluées, l'exhaustivité variait de 47% à 98%. Six variables sur 13 n'étaient pas correctement relevées (<80% d'exhaustivité). Le DEP calculé était indiqué sur 885 (92%) cartes, mais n'était juste que sur 609 (69%) cartes. La variabilité du DEP était notée sur 835 (87%) cartes mais était correctement calculée sur seulement 442 (53%). Seuls 359 (37%) patients ont assisté à leur consultation de contrôle, ce qui signifie que 63% ont été perdus de vue. Il manquait un numéro de téléphone de contact sur 453 (47%) cartes.Conclusion : Cette première étude africaine d'évaluation de l'exhaustivité des données et de l'intégrité des cartes de traitement des patients asthmatiques a identifié des lacunes importantes. Celles-ci affectent la qualité de la prise en charge des patients asthmatiques et l'évaluation des programmes. Il est urgent de prendre des mesures afin de rectifier ces problèmes.

Marco de referencia: Cuatro hospitales distritales del sector público que suministran tratamiento del asma en el estado de Gazeera en Sudán. El registro incompleto de los datos de los pacientes menoscaba directamente la calidad del tratamiento del asma y la evaluación de los programas de atención.Objetivo: Evaluar el carácter integral del llenado de las tarjetas de tratamiento y la exactitud del cálculo del flujo espiratorio máximo (FEM) al confirmar el diagnóstico de asma y evaluar su gravedad.Método: Se examinaron las tarjetas de tratamiento de los pacientes asmáticos en los centros especializados del 2006 al 2012.Resultados: De las 959 tarjetas de tratamiento examinadas, entre 47% y 98% contaban con la información completa de los pacientes. Seis de las 13 variables presentaban un grado de integridad deficiente (menos de 80% de compleción). En 885 tarjetas se había consignado el FEM (92%), pero el cálculo era correcto en solo 609 casos (69%). La variabilidad del FEM se registró en 835 tarjetas (87%), pero su cálculo fue correcto solo en 442 (53%). Solo 359 pacientes (37%) acudieron a una cita de control programada, lo cual corresponde a 63% de pérdidas durante el seguimiento. En 453 tarjetas (47%) faltaba un número telefónico de contacto.Conclusión: El presente fue el primer estudio de evaluación de la compleción y la integridad de los datos de las tarjetas de tratamiento del asma en África y reveló carencias considerables. Esta situación deteriora la calidad del tratamiento de los pacientes con asma y la evaluación de los programas. Es necesario adoptar con urgencia medidas encaminadas rectificar estas deficiencias.

Fostering interest in research: evaluation of an introductory research seminar at hospitals in rural Rwanda.

SETTINGS: Partners In Health Rwanda, in collaboration with the Ministry of Health, leads a multipronged approach to develop research capacity among health workers, particularly in rural areas. OBJECTIVES: To describe the characteristics of participants and to assess the impact of an introductory research seminar series in three district hospitals in rural Rwanda. DESIGN: This was a retrospective cohort study of seminar participants. Data were sourced from personnel records, assessment sheets and feedback forms. RESULTS: A total of 126 participants, including 70 (56%) clinical and 56 (44%) non-clinical staff, attended the research seminar series; 61 (48%) received certification. Among those certified, the median assessment score on assignments was 79%. Participants read significantly more articles at 6 and 12 months (median 2 and 4 respectively, compared to 1 at baseline, P < 0.01). There was also a significant increase (P ⩽ 0.05) in self-reported involvement in research studies (28%, baseline; 59%, 12 months) and attendance at other research training (36%, baseline; 65%, 12 months). CONCLUSION: The introductory research seminar series provided an important opportunity for engagement in research among clinical and non-clinical staff. Such an activity is a key component of a comprehensive research capacity building programme at rural sites, and serves as an entry point for more advanced research training.

Contexte : Partners In Health Rwanda, en collaboration avec le Ministère de la Santé, mène une approche multiple afin de développer les capacités de recherche du personnel de santé, surtout dans les zones rurales.Objectifs : Décrire les caractéristiques des participants et évaluer l'impact d'une série de séminaires d'introduction à la recherche dans trois hôpitaux de district ruraux du Rwanda.Schéma : Etude rétrospective de cohorte des participants au séminaire. Les données ont été recueillies à partir de dossiers personnels, de formulaires d'évaluation et de rétroaction.Résultats : Des 126 participants qui ont assisté à la série de séminaires de recherche, 70 (56%) étaient cliniciens et 56 (44%) personnel non-clinicien. Soixante et un (48%) ont obtenu leur certificat. Parmi ces derniers, le score médian d'évaluation des travaux était de 79%. Les participants lisaient beaucoup plus d'articles à 6 et 12 mois (médiane = 2 et 4 respectivement, comparé à 1 au départ, P < 0,01). On notait également une augmentation significative (P ⩽ 0,05) de l'implication dans des travaux de recherche rapportée par les intéressés eux-mêmes (28% au départ contre 59% à 12 mois) ainsi que de la participation à d'autres formations relatives à la recherche (36% au départ contre 65% à 12 mois).Conclusion : La série de séminaires d'introduction à la recherche a fourni une opportunité majeure d'engagement dans la recherche du personnel clinicien et non clinicien. Une telle activité est un élément clé d'un programme complet de renforcement des capacités de recherche dans les zones rurales et sert de point d'entrée pour des formations à la recherche plus avancées.

Marco de referencia: La organización Partners In Health de Rwanda, en colaboración con el Ministerio de Salud, dirige un proyecto multidimensional de creación de capacidad de investigación, dirigida a los profesionales que se ocupan de la salud, especialmente en las zonas rurales.Objetivos: Describir las características de los participantes y evaluar el efecto de la realización de una serie de seminarios introductorios a la investigación, en tres hospitales distritales de zonas rurales en Rwanda.Método: Fue este un estudio retrospectivo de cohortes de los participantes a los seminarios. Se obtuvieron datos a partir de los registros personales, las hojas de evaluación y los formularios de retroalimentación.Resultados: Participaron a la serie de seminarios 126 personas, de las cuales 70 pertenecían al personal asistencial (56%) y 56 a personal de otras esferas (44%). Sesenta y un participantes recibieron la certificación (48%). De las personas certificadas, la mediana de puntuación de la evaluación fue 79%. Los participantes leyeron más artículos a los seis y a los doce meses de la intervención (mediana = 1 y 4 respectivamente; P < 0,01) que al comienzo de la misma (mediana = 1; P ⩽ 0,05). Se observó además un aumento significativo de la intervención autorreferida en estudios de investigación (28% al comienzo y 59% a los 12 meses) y de la participación en otras capacitaciones científicas (36% al comienzo y 65% a los 12 meses).Conclusión: La serie de seminarios introductorios a la investigación ofreció al personal asistencial y a otros miembros del personal una importante oportunidad de participar en las actividades científicas. Este tipo de intervención constituye un componente primordial del programa integral de creación de capacidad de investigación en los centros rurales y representa una puerta de entrada a las capacitaciones científicas más avanzadas.

Open access for operational research publications from low- and middle-income countries: who pays?

Open-access journal publications aim to ensure that new knowledge is widely disseminated and made freely accessible in a timely manner so that it can be used to improve people's health, particularly those in low- and middle-income countries. In this paper, we briefly explain the differences between closed- and open-access journals, including the evolving idea of the 'open-access spectrum'. We highlight the potential benefits of supporting open access for operational research, and discuss the conundrum and ways forward as regards who pays for open access.

Les articles de journaux en accès libre visent à assurer la dissémination large de nouvelles connaissances et de rendre leur accès libre de façon à pouvoir être utilisées rapidement pour améliorer la santé des populations, surtout dans les pays à revenu faible ou moyen. Dans cet article, nous expliquons briêvement les différences entre les publications à accès limité et à accès libre, notamment l'idée en gestation de « spectre d'accès libre ¼. Nous soulignons les bénéfices potentiels du soutien à l'accès libre pour la recherche opérationnelle et ensuite discutons la question de qui paye pour cet accès et la recherche de solutions.

El propósito de las publicaciones en las revistas de acceso libre es lograr una amplia difusión de los nuevos conocimientos mediante el acceso libre y oportuno, de manera que los avances se puedan aplicar a fin de mejorar la salud de las personas, sobre todo en los países de bajos y medianos ingresos. En el presente artículo se explican brevemente las diferencias entre las revistas de acceso libre y acceso restringido y se analiza además la idea evolutiva del 'espectro del acceso libre'. Se destacan las ventajas que puede ofrecer el respaldo al libre acceso a la investigación operativa y se analiza luego el dilema y las opciones que pueden permitir progresar con respecto a la fuente de financiamiento del libre acceso.