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Problem New drugs for infectious diseases often need to be evaluated in low-resource settings. While people working in such settings often provide high-quality care and perform operational research activities, they generally have less experience in conducting clinical trials designed for drug approval by stringent regulatory authorities. Approach We carried out a capacity-building programme during a multi-centre randomized controlled trial of delamanid, a new drug for the treatment of multidrug-resistant tuberculosis. The programme included: (i) site identification and needs assessment; (ii) achieving International Conference on Harmonization - Good Clinical Practice (ICH-GCP) standards; (iii) establishing trial management; and (iv) Increasing knowledge of global and local regulatory issues. Local setting Trials were conducted at 17 sites in nine countries (China, Egypt, Estonia, Japan, Latvia, Peru, the Philippines, the Republic of Korea and the United States of America). Eight of the 10 sites in low-resource settings had no experience in conducting the requisite clinical trials. Relevant changes Extensive capacity-building was done in all 10 sites. The programme resulted In improved local capacity in key areas such as trial design, data safety and monitoring, trial conduct and laboratory services. Lessons learnt Clinical trials designed to generate data for regulatory approval require additional efforts beyond traditional research-capacity strengthening. Such capacity-building approaches provide an opportunity for product development partnerships to improve health systems beyond the direct conduct of the specific trial. Probleme Les nouveaux medicaments pour le traitement des maladies infectieuses doivent souvent etre evalues dans des pays a faibles ressources. Meme si le personnel qui travaille dans un tel contexte realise souvent des soins et des activites de recherche operationnelle de grande qualite, il est generalement moins experimente pour effectuer des essais cliniques en vue d'obtenir l'approbation des nouveaux medicaments par des autorites de reglementation tres strictes. Approche Nous avons mene un programme de renforcement des capacites a l'occasion d'un essai controle randomise multicentrique du delamanid; un nouveau medicament pour le traitement de la tuberculose multiresistante. Ce programme comprenait: (i) l'identification des sites et l'evaluation des besoins; (ii) l'application des normes de la Conference internationale sur l'harmonisation relatives aux bonnes pratiques cliniques (normes ICH-GCP); (iii) la mise en oeuvre d'une gestion des essais; et (iv) l'amelioration des connaissances sur les aspects reglementaires locaux et internationaux. Environnement local Des essais ont ete realises sur dix-sept sites, repartis dans neuf pays (Chine, Egypte, Estonie, Etats-Unis d'Amerique, Japon, Lettonie, Perou, Philippines et Republique de Coree). Parmi les dix sites implantes dans des pays a faibles ressources, huit n'avaient aucune experience dans la conduite des essais cliniques requis. Changements significatifs Un important renforcement des capacites a ete realise sur l'ensemble des dix sites. Ce programme s'est traduit par une amelioration des capacites locales dans des domaines cles comme la conception des essais, la securite et le controle des donnees, la conduite des essais et les services de laboratoire. Lecons tirees Les essais cliniques concus pour produire des donnees en vue d'obtenir l'approbation reglementaire necessitent des efforts complementaires, qui vont au-dela des activites traditionnelles de renforcement des capacites de recherche. Les approches de ce type visant a renforcer ces capacites offrent une opportunite de partenariat pour le developpement de nouveaux produits en vue d'ameliorer les systemes de sante parallelement a la realisation directe des essais requis. Problema Los nuevos farmacos para enfermedades infecciosas a menudo necesitan ser probados en emplazamientos con pocos recursos. Aunque los profesionales que trabajan en dichos emplazamientos ofrezcan una atencion de alta calidad y lleven a cabo una actividad de investigacion operativa, en general no tienen la experiencia suficiente para llevar a cabo los ensayos clinicos disenados para aprobarfarmacos segun dictan los estrictos organismos de reglamentacion. Enfoque Se llevo a cabo un programa de fortalecimiento de la capacidad durante un ensayo multlcentrico controlado aleatorlzado de delamanid, un nuevo farmaco para el tratamiento de la tuberculosis multirresistente. El programa incluia: (i) identificacion del emplazamiento y evaluacion de las necesidades; (ii) cumplimiento con las normas de buenas practicas clinicas (BPC) de la Conferencia Internacional sobre Armonizacion (ICH); (iii) establecimiento de una gestion de los ensayos; y (iv) incremento del conocimiento de los aspectos regulatenos a nivel global y local. Marco regional Los ensayos se llevaron a cabo en 17 emplazamientos de nueve paises (China, Egipto, Estados Unidos de America, Estonia, Filipinas, Japon, Letonia, Peru y Republica de Corea). Ocho de los 10 lugares con pocos recursos no tenian experiencia alguna en como dirigir los ensayos clinicos necesarios. Cambios importantes Se ha aumentado considerablemente la capacidad en todos los 10 emplazamientos. El programa se tradujo en una mejor capacidad local en aspectos clave como el diseno del ensayo, la seguridad y la supervision de los datos, la realizacion de los ensayos y los servicios de los laboratorios. Lecciones aprendidas Los ensayos clinicos disenados para generar datos para una aprobacion normativa requieren esfuerzos adicionale mas alla del ya tradicional refuerzo de las capacidades de investigado Dichos enfoques de aumento de la capacidad brindan una oportunidf para que las asociaciones para el desarrollo del producto mejore los sistemas sanitarios, mas alla de la realizacion directa del ensay especifico., Introduction Traditional research capacity-building efforts tend to focus on post-approval clinical studies and operational research, (1) rather than initial regulatory approval of new medicines. (2,3) New medicines are needed for [...]

The World Health Organization (WHO) estimates that one fourth of the world's population has Mycobacterium tuberculosis infection and is at risk of developing active tuberculosis. (1) The current standard treatment [...]

Objective WHO&apos;s new Global Plan to Stop T8 2006-2015 advises countries with a high burden of tuberculosis (TB) to expand case-finding in the private sector as well as services for patients with HIV and multidrug-resistant TB (MDR-TB). The objective of this study was to evaluate these strategies in Thailand using data from the Thailand TB Active Surveillance Network, a demonstration project begun in 2004. Methods In October 2004, we began contacting public and private health-care facilities monthly to record data about people diagnosed with TB, assist with patient care, provide HIV counselling and testing, and obtain sputum samples for culture and susceptibility testing. The catchment area included 3.6 million people in four provinces. We compared results from October 2004-September 2005 (referred to as 2005) to baseline data from October 2002-September 2003 (referred to as 2003). Findings In 2005, we ascertained 5841 TB cases (164/100 000), including 2320 new smear-positive cases (65/100 000). Compared with routine passive surveillance in 2003, active surveillance increased reporting of all TB cases by 19% and of new smear-positive cases by 13%. Private facilities diagnosed 634 (11%) of all TB cases. In 2005, 1392 (24%) cases were known to be HIV positive. The proportion of cases with an unknown HIV status decreased from 66% (3226/4904)in 2003 to 23% (1329/5841) in 2005 (P< 0.01). Of 4656 pulmonary cases, mycobacterial culture was performed in 3024 (65%) and MDR-TB diagnosed in 60 (1%). Conclusion In Thailand, piloting the new WHO strategy increased case-finding and collaboration with the private sector, and improved HIV services for TB patients and the diagnosis of MDR-TB. Further analysis of treatment outcomes and costs is needed to assess this programme&apos;s impact and cost effectiveness. Objectif Le nouveau Plan mondial << Halte a la tuberculose >> 2006-2015 de l&apos;OMS conseille aux pays supportant une forte charge de tuberculose (TB) de renforcer la participation du secteur prive dans le depistage de cette maladie et de developper davantage les services destines aux personnes porteuses du VlH et atteintes d&apos;une tuberculose a bacille multiresistant (TB-MR). La presente etude a pour objectif d&apos;evaluer la mise en oeuvre de ces strategies en Thailande a partir des donnees fournies par le Thailand TB Active Surveillance Network (reseau de surveillance active de la tuberculose en Thailande), projet experimental lance en 2004. Methodes En octobre 2004, nous avons etabii des contacts avec des etablissements de soins de sante publics et prives pour recueillir des donnees sur les personnes diagnostiquees comme tuberculeuses, aider a la delivrance de soins de sante, fournir des prestations de conseil et de depistage concernant le VIH et obtenir des echantillons d&apos;expectorations en vue de pratiquer des cultures et des tests de pharmacosensibilite. La zone de desserte comptait 3,6 millions d&apos;habitants repartis dans quatre provinces. Nous avons compare les resultats pour la periode octobre 2004-septembre 2005 (designee par 2005) avec des donnees de reference pour la periode octobre 2002-septembre 2003 (designee par 2003). Resultats En 2005, nous avons enregistre 5841 cas de TB (164/100 000), dont 2320 nouveaux cas de TB a frottis positif (65/100 000). Par rapport aux resultats fournies par la surveillance passive systematique en 2003, la surveillance active apermis une augmentation de la notification de 19 % pour le nombre total de cas de TB et de 13 % pour le nombre de nouveaux cas de TB a frottis positif. Les etablissements prives ont diagnostique 634 (11%) des nouveaux cas de TB. En 2005, 1392 (24%) cas de TB etaient connus comme seropositifs pour le VIH. La proportion de cas de TB avec un statut VIH inconnu est passee de 66 % (3226/4904) en 2003 a 23 % (1329/5841) en 2005 (p < 0,01). Parmi les 4656 cas de TB pulmonaire, 3024 (65%) ont fait l&apos;objet d&apos;une culture mycobacterienne et 60 (1%) ont ete diagnostiques comme atteints d&apos;une TB-MR. Conclusion En Thailande, l&apos;experimentation de la nouvelle strategie OMS a permis d&apos;accroitre le nombre de cas de TB depistes, de renforcer la collaboration avec le secteur prive et d&apos;ameliorer les services lies au VlH a l&apos;intention des personnes tuberculeuses, ainsi que le diagnostic des TB-MR. Une analyse plus poussee des resultats et des couts therapeutiques s&apos;impose pour evaluer l&apos;impact du programme et son rapport cout-efficacite. Objetivo El nuevo Plan Mundial de la OMS para Detener la Tuberculosis 2006-2015 aconseja a los paises que presentan una alta carga de la enfermedad que amplien la busqueda de casos en el sector privado, asi como los servicios destinados a los pacientes con infeccion por VIH y tuberculosis multirresistente (TB-MR). El objetivo del estudio fue evaluar esas estrategias en Tailandia utilizando los datos de la Red de Vigilancia Activa de la Tuberculosis del pais, un proyecto de demostracion iniciado en 2004. Metodos En octubre de 2004 empezamos aponernos en contacto cada mes con servicios de atencion sanitaria publicos y privados a fin de registrar los datos pertinentes sobre las personas con diagnostico de tuberculosis, contribuir a la asistencia a los enfermos, ofrecer asesoramiento y pruebas del VIH y obtener muestras de esputo para la realizacion de cultivos y pruebas de sensibilidad. La zona de captacion abarcaba a 3,6 millones de personas en cuatro provincias. Comparamos los resultados de octubre de 2004 a septiembre de 2005 (en adelante 2005) con los datos de partida correspondientes ai periodo de octubre de 2002 a septiembre de 2003 (en adelante 2003). Resultados En 2005 evaluamos 5841 casos de tuberculosis (164/100 000), incluidos 2320 casos baciliferos nuevos (65/ 100 000). En comparacion con la vigilancia pasiva sistematica de 2003, la vigilancia activa aumento la notificacion de todos los casos de tuberculosis en un 19%, y de los casos baciliferos nuevos en un 13%. Los servicios privados diagnosticaron el 11% (634) de todos los casos de tuberculosis. En 2005 se detectaron 1392 (24%) casos VIH-positivos. La proporcion de casos con serologia VIH desconocida disminuyo del 66% (3226/4904) en 2003 al 23% (1329/5841) en 2005 (p < 0,01). De 4656 casos pulmonares, se realizo un cultivo micobacteriano en 3024 (65%), y se diagnostico TB-MR en 60 (1%). Conclusion En Tailandia, la aplicacion piloto de la nueva estrategia de la OMS aumento la busqueda de casos y la colaboracion con el sector privado, y ademas mejoro los servicios de VIH para los enfermos tuberculosos y el diagnostico de TB-MR. Es necesario seguir analizando los resultados terapeuticos y los costos a fin de evaluar el impacto y la costoeficacia de este programa., Background Tuberculosis (TB) remains one of the world's leading causes of severe illness and death, particularly in developing countries. Since 1993, efforts to control TB have focused on a strategy [...]

Antiretroviral therapy (ART) is lifesaving in patients with advanced HIV infection, but the magnitude of benefit in HIV-infected patients receiving tuberculosis (TB) treatment remains uncertain, and population-based data from developing [...]

Objective. To describe trends and highlight epidemiologic and clinical characteristics of childhood tuberculosis (TB) in the United States. Methods. All verified TB cases reported to the national TB surveillance system from 1993 to 2001 were included. A child was defined as a person younger than 15 years. Results. A total of 11 480 childhood TB cases were reported. Case rates (TB cases/100 000 population) in all children declined from 2.9 (n = 1663) in 1993 to 1.5 (n = 931) in 2001. Among children, those who were younger than 5 years had the highest rate. California, Texas, and New York accounted for 48% of all childhood TB cases. In 2001, TB case rates were higher for foreign-born (12.2) than US-born children (1.1). Hispanic and non-Hispanic black children accounted for nearly three quarters of all cases. Twenty-four percent of children with TB were foreign-born children, with the largest number originating from Mexico (39.8%), the Philippines (8.6%), and Vietnam (5.7%). Most children had evidence of pulmonary TB disease (78.9%). Among culture-positive cases without previous TB, drug resistance to at least isoniazid was 7.3% and to isoniazid and rifampin was 1.6%. In 1999, 82.9% of children received directly observed therapy for at least part of their treatment and 94.8% completed treatment. Conclusions. Although the overall TB case number among children is declining in the United States, certain groups of children (eg, younger children, racial and ethnic minorities, foreign-born) are at higher risk for TB. As the United States moves toward the elimination of TB, future efforts should endeavor to prevent all cases of childhood TB. Pediatrics 2004;114:333-341; epidemiology, tuberculosis, children, pediatrics., ABBREVIATIONS. TB, tuberculosis; LTBI, latent tuberculosis infection; HIV, human immunodeficiency virus; RR, relative risk; CI, confidence interval; CDC, Centers for Disease Control and Prevention; TST, tuberculin skin test; INH, isoniazid; [...]

To improve multidrug-resistant tuberculosis (MDR-TB) detection, we successfully introduced the rpoB gene mutation line probe assay into the national laboratory in Latvia, a country with epidemic MDR-TB. The assay detected [...]

Abstract Background In Southeast Asia, HIV-infected patients frequently die during TB treatment. Many physicians are reluctant to treat HIV-infected TB patients with anti-retroviral therapy (ART) and have questions about the added value of opportunistic infection prophylaxis to ART, the optimum ART regimen, and the benefit of initiating ART early during TB treatment. Methods We conducted a multi-center observational study of HIV-infected patients newly diagnosed with TB in Thailand. Clinical data was collected from the beginning to the end of TB treatment. We conducted multivariable proportional hazards analysis to identify factors associated with death. Results Of 667 HIV-infected TB patients enrolled, 450 (68%) were smear and/or culture positive. Death during TB treatment occurred in 112 (17%). In proportional hazards analysis, factors strongly associated with reduced risk of death were ART use (Hazard Ratio [HR] 0.16; 95% confidence interval [CI] 0.07–0.36), fluconazole use (HR 0.34; CI 0.18–0.64), and co-trimoxazole use (HR 0.41; CI 0.20–0.83). Among 126 patients that initiated ART after TB diagnosis, the risk of death increased the longer that ART was delayed during TB treatment. Efavirenz- and nevirapine-containing ART regimens were associated with similar rates of adverse events and death. Conclusion Among HIV-infected patients living in Thailand, the single most important determinant of survival during TB treatment was use of ART. Controlled clinical trials are needed to confirm our findings that early ART initiation improves survival and that the choice of non-nucleoside reverse transcriptase inhibitor does not.

Abstract Background Of the 9.2 million new TB cases occurring each year, about 10% are in children. Because childhood TB is usually non-infectious and non-fatal, national programs do not prioritize childhood TB diagnosis and treatment. We reviewed data from a demonstration project to learn more about the epidemiology of childhood TB in Thailand. Methods In four Thai provinces and one national hospital, we contacted healthcare facilities monthly to record data about persons diagnosed with TB, assist with patient care, provide HIV counseling and testing, and obtain sputum for culture and susceptibility testing. We analyzed clinical and treatment outcome data for patients age < 15 years old registered in 2005 and 2006. Results Only 279 (2%) of 14,487 total cases occurred in children. The median age of children was 8 years (range: 4 months, 14 years). Of 197 children with pulmonary TB, 63 (32%) were bacteriologically-confirmed: 56 (28%) were smear-positive and 7 (4%) were smear-negative, but culture-positive. One was diagnosed with multi-drug resistant TB. HIV infection was documented in 75 (27%). Thirteen (17%) of 75 HIV-infected children died during TB treatment compared with 4 (2%) of 204 not known to be HIV-infected (p < 0.01). Conclusion Childhood TB is infrequently diagnosed in Thailand. Understanding whether this is due to absence of disease or diagnostic effort requires further research. HIV contributes substantially to the childhood TB burden in Thailand and is associated with high mortality.

A sensitive and accurate tuberculosis (TB) serodiagnostic test would aid in the control of TB, but results of current tests are relatively unreliable for persons infected with human immunodeficiency virus (HIV). We evaluated a new prototype immunochromatographic strip test and 5 commercially available serodiagnostic TB tests in a prospective study comprised of 465 consecutively enrolled patients with suspected TB from 2 hospitals in Botswana. Consenting adults underwent HIV testing, &ges;2 sputum smears and cultures, and mycobacterial blood culture. Patients were defined as having TB on the basis of any positive smear or culture. Between January and September 2002, 465 of 498 consecutive patients consented to enrollment. A total of 384 patients (83%) were infected with HIV, and 175 (38%) had TB; the mycobacterial blood culture was the sole source of diagnosis for 26 patients (15%) with TB. Among the tests evaluated, the sensitivity was 0%- 63%, the specificity was 39%-99%, the positive predictive value was 0%-39%, and the negative predictive value was 63%-65%. We conclude that the serodiagnostic tests evaluated in this study lacked sufficient sensitivity as sole tests for TB in this population. [ABSTRACT FROM AUTHOR]

For many individuals from developing countries, infection with Mycobacterium tuberculosis is almost inevitable. In recent years, there has been an increase in the number of immigrants and refugees from some of these countries, and thus the proportion of these individuals among newly diagnosed cases of tuberculosis has increased. The identification of these patients and the proper management of their cases are important public health priorities. Dr. Nancy Binkin and her colleagues review the data on the epidemiology of tuberculosis in immigrants and refugees and describe the available screening and evaluation programs overseas and in this country. They also highlight the importance of maintaining and expanding health care services in this country that are appropriate and welcoming to foreign-born persons. They clearly demonstrate that the control of tuberculosis in the United States will require a coordinated effort that transcends its borders. —Wafaa El-Sadr Division of Infectious Diseases, Harlem Hospital Center, New York, New York Chair, IDSA Tuberculosis Committee The number of reported cases of tuberculosis (TB) in foreign-born persons in the United States during 1995 was 8,042, 36% of the national total. The overseas screening of immigrants and refugee visa applicants, which relies on a chest radiograph and smear microscopy, is designed to identify future U.S. residents who have active TB or who are at high risk for TB. In this commentary, we summarize current policies and review retrospective evaluations of the screening system currently in place. The system appears to detect most persons who have active TB at the time of screening. However, active TB is actually diagnosed in <15% of persons who are identified by screening as having suspected TB and who are evaluated in the United States. To improve the system, more sensitive and specific techniques as well as improved means of data transmission to state and local health departments are needed. [ABSTRACT FROM PUBLISHER]