Showing papers in "International Journal of Tuberculosis and Lung Disease in 2006"

False-positive tuberculin skin tests: what is the absolute effect of BCG and non-tuberculous mycobacteria?

Abstract: SUMMARY of Epidemiology & Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada BACKGROUND: Despite certain drawbacks, the tuberculin skin test (TST) remains in widespread use. Important advantages of the TST are its low cost, simplicity and interpretation based on extensive published literature. However, TST specificity is reduced by bacille Calmette-Guerin (BCG) vaccination and exposure to non-tuberculous mycobacteria (NTM). METHODS: To estimate TST specificity, we reviewed the published literature since 1966 regarding the effect of BCG vaccination and NTM infection on TST. Studies selected included healthy subjects with documented BCG vaccination status, including age at vaccination. Studies of NTM effect had used standardised NTM antigens in healthy subjects. RESULTS: In 24 studies involving 240 203 subjects BCGvaccinated as infants, 20 406 (8.5%) had a TST of 10� mm attributable to BCG, but only 56/5639 (1%) were TST-positive if tested � 10 years after BCG. In 12 studies of 12 728 subjects vaccinated after their first birthday, 5314 (41.8%) had a false-positive TST of 10� mm, and 191/898 (21.2%) after 10 years. Type of tuberculin test did not modify these results. In 18 studies involving 1 169 105 subjects, the absolute prevalence of false-positive TST from NTM cross-reactivity ranged from 0.1% to 2.3% in different regions. CONCLUSIONS: The effect on TST of BCG received in infancy is minimal, especially � 10 years after vaccination. BCG received after infancy produces more frequent, more persistent and larger TST reactions. NTM is not a clinically important cause of false-positive TST, except in populations with a high prevalence of NTM sensitisation and a very low prevalence of TB infection.

Guidance for national tuberculosis programmes on the management of tuberculosis in children. Chapter 2: anti-tuberculosis treatment in children.

Abstract: The management of children with TB should be in line with the Stop TB Strategy, taking into consideration the particular epidemiology and clinical presentation of TB in children. Obtaining good treatment outcomes depends on the application of standardised treatment regimens according to the relevant diagnostic category, with support for the child and carer that maximises adherence to treatment. A recent development in treatment recommendations is that, following a comprehensive literature review, ethambutol is now considered safe in children at a dose of 20 mg/kg (range 15-25 mg/kg) daily. Critical areas for further research include the optimal formulations and dosing of first- and second-line TB drugs and new drug development.

Differentiation of Mycobacterium tuberculosis complex by PCR amplification of genomic regions of difference.

Abstract: Differentiation of members of the Mycobacterium tuberculosis complex by conventional mycobacteriological methods is time consuming, making surveillance of species-specific disease difficult A two-step, multiplex polymerase chain reaction (PCR) method based on genomic regions of difference (RD1, RD1(mic), RD2(seal), RD4, RD9 and RD12) was developed for the differentiation of M canettii, M tuberculosis, M africanum, M microti, M pinnipedii, M caprae, M bovis and M bovis BCG The size of the respective multiplex PCR amplification products corresponded to the presence of the different M tuberculosis complex members This method allows for rapid differentiation, making it suitable for routine laboratories and surveillance purposes

Delayed tuberculosis diagnosis and tuberculosis transmission

Abstract: CONTEXTE : Les patients tuberculeux (TB) et leurs contacts etroits declares au Departement de Sante et d'Hygiene Mentale du Maryland entre le 1 er juin 2000 et le 30 novembre 2001 OBJECTIFS: Une etude prospective recente a trouve que 49% des patients atteints de TB pulmonaire avaient des delais totaux de traitement ≥90 jours Cette cohorte a ete analysee pour determiner l'association entre le delai total du traitement et la transmission de la TB SCHEMA: Les donnees de patients tuberculeux ont ete colligees au sein d'une etude prospective de cohorte; des donnees de contacts ont ete rassemblees a partir des departements locaux de sante RESULTATS: Les 310 contacts etroits de 54 patients nes aux Etats-Unis et 393 contacts de patients nes a l'etranger ont recu des tests cutanes tuberculiniques (TST) Parmi les contacts des patients nes aux Etats-Unis et dont le delai total de traitement etait ≥90 jours, 40% avaient un TST positif par comparaison avec 24% chez les patients dont les delais etaient plus courts (aOR 2,34; P = 0,03) D'autres facteurs lies aux patients sont associes avec la positivite du TST parmi les contacts de cas nes aux Etats-Unis; il s'agit de la race noire (aOR 3,03; P = 0,05), de la positivite des frottis d'expectoration pour les bacilles acido-resistants (aOR 3,29; P = 0,01) ainsi que des cliches thoraciques comportant des cavites (aOR 3,11; P = 0,01) On n'a pas trouve d'association entre les patients nes a l'etranger et le risque de positivite du TST chez leurs contacts CONCLUSION: Chez les patients nes aux Etats-Unis, le retard du diagnostic de la TB s'accompagne d'une transmission plus importante de l'infection vers les contacts; celui-ci pourrait etre utilise independamment d'autres facteurs-index chez les patients pour identifier les contacts ayant le plus grand risque d'infection tuberculeuse

An epidemiological evaluation of risk factors for tuberculosis in South India: a matched case control study.

Abstract: CONTEXTE : On ne connait que peu de donnees sur les facteurs de risque associes a la tuberculose (TB) en Inde. OBJECTIFS: Evaluer les facteurs de risque sociodemographiques potentiels pour la TB. SCHEMA: Etude cas-controle appariee. Les cas etaient tous de nouveaux diagnostics de TB pulmonaire se presentant comme patients externes a 1'Hopital du St John's Medical College a Bangalore, Inde, entre octobre 2001 et octobre 2003. Les controles, un par cas (n = 189) etaient apparies pour l'âge et le sexe parmi les membres de la famille accompagnant des patients non-tuberculeux a l'hopital. RESULTATS : Les facteurs de risque significatifs ont ete un faible niveau d'education (OR 0,30 ; IC95% 0,11-0,82), le fait de ne pas disposer d'une cuisine separee (OR 3,26 ; IC95% 1,25-8,46) et une maladie chronique, particulierement le diabete (OR 2,44; IC95% 1,17-5,09). A l'analyse multivariee, on n'a pas trouve de relation significative avec un revenu eleve, avec le fait d'utiliser des combustibles vegetaux pour cuisiner et avec des antecedents de consommation de tabac et d'alcool. Les patients avaient un risque respectivement 11 et sept fois superieur d'avoir un index de masse corporelle <18,5 (IC95% 5,62-21,98) et une circonference a mibras <24 cm (IC95% 3,87-11,89). CONCLUSIONS: Dans notre etude, la TB est associee a un faible niveau d'education, au type de cuisine et au diabete, ce qui reflete l'interaction complexe entre des maladies non transmissibles, l'urbanisation et un climat economique changeant a Bangalore. Les relations entre la TB, l'utilisation de combustibles vegetaux et les differences par sexe liees a l'exposition aux combustibles meritent une exploration complementaire. Cette etude souligne le mediocre etat nutritionnel des patients.

Tuberculosis in patients receiving anti-TNF agents despite chemoprophylaxis.

Abstract: CONTEXTE : Une inquietude majeure concernant l'utilisation des inhibiteurs du TNF-a est leur potentialite d'accroissement du risque d'infections opportunistes, particulierement la tuberculose (TB). OBJECTIF: Estimer l'incidence de la TB active chez les patients atteints de maladie rhumatismale sous traitement par des medicaments anti-TNF et evaluer l'efficience d'un regime de chimioprophylaxie antituberculeuse. SCHEMA: Etude retrospective des dossiers de 613 patients atteints de maladies rhumatismales qui avaient recu un medicament anti-TNF (etanercept, infliximab et adalimumab) entre juillet 2000 et juin 2004 a l'Universite Aristotle de Thessalonique, Grece. Tous les patients ont eu un test cutane tuberculinique (TST) et un cliche thoracique (CXR) postero-anterieur avant la mise en route du traitement anti-TNF. Lorsque c'etait indique (TST ≥10 mm et/ou lesions fibrotiques au CXR) on a instaure un traitement pour la TB latente (soit 6 mois d'isoniazide [INH], soit 3 mois d'INH et de rifampicine). Le traitement par un agent anti-TNF a ete remis en route 2 mois plus tard. RESULTATS: Les criteres pour la chimioprophylaxie ont ete remplis par 45 patients, mais seulement 36 d'entre eux ont ete correctement traites. Une TB active s'est developpee chez 11 patients 2 a 35 mois apres le debut du traitement anti-TNF. Chez six patients, la localisation de la TB a ete pulmonaire et chez cinq extrapulmonaire. Huit d'entre eux avaient recu l'infliximab et trois l'adalimumab. CONCLUSION: L'incidence de la TB active dans la population de cette etude a ete estimee a 449 cas per 100000 population par an. La chimioprophylaxie anti-tuberculeuse n'a rencontre qu'un succes preventif partiel chez ces patients.

Influence of diabetes on manifestations and treatment outcome of pulmonary tb patients

Abstract: OBJECTIF: Comprendre l'influence du diabete sur les aspects cliniques et bacteriologiques ainsi que sur les resultats du traitement chez les patients atteints de tuberculose pulmonaire (TBP). CONTEXTE ET SCHEMA: Les dossiers de 692 cas consecutifs de TBP a bacilloscopie positive admis a l'hopital de reference de Riad en Arabie Saoudite ont ete revus retrospectivement. Les caracteristiques de 187 patients atteints en outre de diabete sucre (groupe TBP-DM) ont ete compares a celles de 505 patients sans diabete sucre (groupe TBP). RESULTATS: Dans le groupe TBP-DM, 65,2% des patients avaient de nombreux bacilles acido-resistants a la bacilloscopie des expectorations par comparaison avec 54,1% dans le groupe TBP (P = 0,008). Parmi les nouveaux cas TBP-DM, la prevalence de la resistance a n'importe quel medicament antituberculeux est plus faible (6,4% vs. 16,0%, P = 0,007) ; les taux de negativation des expectorations sont plus eleves a la fin de 3 mois de traitement dans le groupe TBP-DM que dans le groupe TBP (98,9% vs. 94,7%, P = 0,013). Les resultats favorables (guerison/traitement acheve), les echecs, les deces et les perdus de vue sont comparables dans les deux groupes de patients (P = 0,7005). CONCLUSIONS: Chez les patients TBP-DM, la charge bacillaire avant traitement est plus elevee, la prevalence de la resistance aux medicaments antituberculeux est plus faible et les taux de negativation des expectorations sont legerement superieurs a la fin de 3 mois par comparaison avec les patients non diabetiques. L'association avec le diabete n'aggrave pas le resultat final du traitement chez les patients atteints de TBP.

Early and extended early bactericidal activity of levofloxacin, gatifloxacin and moxifloxacin in pulmonary tuberculosis

Abstract: OBJECTIF: Evaluer l'activite bactericide precoce (EBA) des nouvelles fluoroquinolones (levofloxacine, gatifloxacine et moxifloxacine) chez les patients atteints de tuberculose pulmonaire (TBP). SCHEMA : Essai ouvert randomise. Quarante adultes atteints d'une TBP recemment diagnostiquee et a bacilloscopie positive ont ete attribues a raison de 10 par bras soit a l'isoniazide (INH) 300 mg, soit a la levofloxacine 1000 mg, a la gatifloxacine 400 mg ou a la moxifloxacine 400 mg par jour pendant 7 jours. On a recueilli des expectorations pour culture quantitative pendant 2 jours avant la mise en route de la monotherapie et chaque jour au cours des 7 jours de monotherapie. L'activite bactericide a ete estimee en mesurant la diminution du nombre de bacilles au cours des 2 premiers jours (EBA 0-2) et au cours des 5 derniers jours de la monotherapie (EBA prolongee, EBA 2-7). Le personnel du laboratoire ignorait le traitement attribue. RESULTATS: L'EBA 0-2 de l'INH (0.67 log 10 cfu/ml/ jour) est plus elevee que celle de la moxifloxacine (0.33 log 10 cfu/ml/jour) et de la gatifloxacine (0.35 log 10 cfu/ ml/jour), mais pas que celle de la levofloxacine a 1000 mg par jour (0.45 log 10 cfu/ml/jour) (P = 0.14). L'activite bactericide entre les jours 2 et 7 est similaire pour les trois fluoroquinolones. Dans une comparaison combinant les fluoroquinolones, l'EBA 2-7est superieure a celle de l'INH. CONCLUSION: La moxifloxacine, la gatifloxacine et les fortes doses de levofloxacine ont d'excellentes EBA qui ne sont que legerement inferieures a l'INH et elles ont une EBA prolongee plus importante. Ces medicaments meritent des etudes complementaires dans le traitement de la TB a germes sensibles.

The burden of childhood tuberculosis and the accuracy of community-based surveillance data.

Abstract: CONTEXTE: La qualite des donnees epidemiologiques concernant la tuberculose (TB) infantile est compromise par une surveillance inadequate et par les difficultes de diagnostic. OBJECTIF: Documenter l'incidence de la TB de l'enfant et evaluer la precision des donnees de surveillance basees sur la collectivite dans un contexte a haute prevalence. METHODES: Cette etude prospective d'observation a ete menee entre fevrier 2003 et octobre 2004 dans cinq polycliniques de soins de sante primaires a Cape Town, Afrique du Sud. Une surveillance complete a ete menee pour s'assurer que tous les enfants âges de moins de 13 ans et traites pour TB avaient bien ete inclus. RESULTATS: Au cours de la periode d'etude, 443 enfants âges de <13 ans ont recu un traitement antituberculeux. Parmi ceux-ci, 389 (87,8%) avaient ete inscrits dans le registre de traitement de la TB. L'incidence de la TB, calculee a partir du registre de traitement de la TB, a ete de 441/100.000 par an parmi les enfants et de 845/ 100.000 par an parmi les adultes. Cinquante-quatre enfants traites pour TB n'etaient pas inscrits dans le registre de traitement de la TB, et parmi ceux-ci se trouvaient 21 des 28 (75%) enfants atteints de TB grave. DISCUSSION: Les enfants âges de <13 ans ont represente 13,7% du fardeau total de TB. L'incidence chez les enfants est superieure a la moitie (52%) de celle enregistree chez les adultes. Les donnees de surveillance basees sur la collectivite n'ont pas inclus la majorite des enfants atteints d'une maladie grave. La precision des donnees de surveillance est une consideration importante lorsqu'il s'agit de decrire l'epidemiologie de la TB de l'enfant ou de mesurer les succes des interventions de sante publique.

Diabetes mellitus is strongly associated with tuberculosis in Indonesia.

Abstract: SETTING: Diabetes mellitus is a known risk factor for tuberculosis (TB), but no studies have been reported from South-East Asia, which has a high burden of TB and a rapidly growing prevalence of diabetes. OBJECTIVE: To examine if and to what extent diabetes is associated with an increased risk of TB in an urban setting in Indonesia. DESIGN: Case-control study comparing the prevalence of diabetes mellitus (fasting blood glucose level >126 mg/dl) among newly diagnosed pulmonary TB patients and matched neighbourhood controls. RESULTS: Patients and control subjects had a similar age (median 30 years) and sex distribution (52% male), but malnutrition was more common among TB patients (median body mass index 17.7 vs. 21.5 kg/m2). HIV infection was uncommon (1.5% of patients). Diabetes mellitus was present in 60 of 454 TB patients (13.2%) and 18 of 556 (3.2%) control subjects (OR 4.7; 95%CI 2.7-8.1). Adjustment for possible confounding factors did not reduce the risk estimates. Following anti-tuberculosis treatment, hyperglycaemia reverted in a minority (3.7%) of TB patients. CONCLUSION: Diabetes mellitus is strongly associated with TB in young and non-obese subjects in an urban setting in Indonesia. This may have implications for TB control and patient care in this region.

The spectrum of disease in children treated for tuberculosis in a highly endemic area.

Abstract: Children contribute a substantial proportion of the global tuberculosis (TB) caseload particularly in endemic areas where little is known about their spectrum of disease. The objective was to document the complete disease spectrum with relevant age- and HIV-related differences in children treated for TB in a highly endemic community. A prospective descriptive study was conducted from February 2003 to October 2004 at five primary health care clinics in Cape Town South Africa including all children (< 13 years of age) treated for TB. In total 439 children received anti-tuberculosis treatment. The spectrum of disease included 85 (19.4%) not TB 307 (86.7%) intra-thoracic TB and 72 (20.3%) extra-thoracic TB (25 [5.7%] with co-existing intra- and extra-thoracic disease were included in both groups). In non-HIV-infected children disseminated (miliary) disease (9/11 81.8%) and tuberculous meningitis (TBM) (10/13 76.9%) were predominantly documented in children < 3 years of age. In HIV-infected children complicated Ghon focus and disseminated (miliary) disease were significantly more common (6/25 24.0%) than in non-HIV-infected children (12/414 2.9%) (OR 10.9 95%CI 3.2-35.9). This study describes the complete disease spectrum observed in children treated for TB in a highly endemic area. Children suffered significant morbidity with most severe disease recorded in very young and/or HIV-infected children. (authors)

Comparison of mantoux skin test with three generations of a whole blood IFN-gamma assay for tuberculosis infection.

Abstract: CONTEXTE: Une ville rurale d'Afrique du Sud. OBJECTIF: Comparer les performances des tests QuantiFERON avec le test cutane tuberculinique (TST) pour identifier l'infection tuberculeuse latente (LTBI) dans une collectivite a haute prevalence de tuberculose (TB). SCHEMA : Lors d'une etude transversale chez des adultes bien portants, nous avons applique le TST et pris du sang pour trois generations de tests QuantiFERON. RESULTATS : Parmi les 358 participants dont les resultats ont ete analyses, 291 (81%) avaient un TST positif avec induration ≥10 mm, et 187 (52%) avec une induration ≥15 mm. Le test QuantiFERON-TB a ete positif dans 215 cas (60%), le QuantiFERON-TB Gold dans 137 cas (38%) et le QuantiFERON-TB Gold (Methode en tube) dans 201 cas (56%). Il y a peu de concordances entre le TST et les tests QuantiFERON ainsi qu'entre les differentes generations des tests QuantiFERON (κ = 0,12-0,50). Dans le sous-groupe porteur d'indurations du TST ≥15 mm, 30 (56%) avaient des tests QuantiFERON negatifs. Toutefois, des tests QuantiFERON positifs sont associes avec le sexe masculin, chez qui l'incidence de la TB est plus elevee dans cette zone. CONCLUSION: Nous avons demontre une faible concordance entre le TST et les differents tests QuantiFERON pour le diagnostic de la LTBI. La discordance surprenante entre le QuantiFERON-TB Gold et la methode en tube du QuantiFERON-TB Gold impose une investigation complementaire.

Treatment of multidrug-resistant tuberculosis: evidence and controversies.

Abstract: In the last decade, multidrug-resistant tuberculosis (MDR-TB, defined as resistance to at least isoniazid and rifampicin) has become an epidemiological issue of first priority at the global level Case management needs to be simplified and standardised, as in many countries MDR-TB cases cannot receive individualised attention from specialist physicians However, before any decision can be made on standardisation, a careful analysis must first be made of the evidence and controversies behind the various published recommendations Unfortunately, the controversies outweigh the evidence The difficulties lie not only in the absence of controlled trials to validate specific recommendations, but also in the very different and even contradictory results found in the literature It is therefore essential to analyse these discrepancies before developing rational, uniform recommendations The analysis should encompass the most essential and controversial issues regarding the management of MDR-TB patients: 1) confirmation of diagnosis in a suspected MDR-TB patient, and determination of the value of drug susceptibility testing; 2) the number of anti-tuberculosis drugs required to treat MDR-TB; 3) the most rational use of effective drugs against tuberculosis; 4) the advisable length of parenteral drug administration or of the initial phase of treatment; 5) the contribution of surgery to the management of MDR-TB patients; and 6) the optimal regimen for treating MDR-TB: standardised vs individualised regimens The evidence and controversies regarding each of the above questions are analysed with the aim of facilitating decision making in the treatment of these complex patients

Targets for global tuberculosis control

Abstract: The United Nations Millennium Development Goals (MDGs) have added to the suite of targets and indicators used to evaluate progress in tuberculosis (TB) control. This paper reviews the history of target setting for TB control and lays out the complete set of indicators and targets that will guide TB control through to 2015, the target year for all MDGs.

Ethambutol dosage for the treatment of children: literature review and recommendations.

Abstract: The currently recommended daily dose of ethambutol (EMB) for the treatment of tuberculosis (TB) in children varies from a maximum daily dose of 15 mg/kg body weight daily (without a range) to 15-20 mg/kg and 20 mg/ kg (range 15-25 mg/kg). Published evidence relating to the dosage, toxicity and pharmacokinetics of EMB in children and adults is reviewed and a dose of EMB for use in childhood is recommended. Using key words 'ethambutol', 'childhood', 'TB', 'pharmacokinetics', 'bioavailability' and 'toxicity', Medline searches were conducted; cross-references were sought from original papers, books and conference proceedings dating from 1961. When English summaries were available, data were extracted from papers in languages other than English. EMB has a dose-related efficacy best seen when given to adults alone or with a single other drug. Together with isoniazid (INH), a dose of 15 mg/kg EMB gave better results than 6 mg/kg, and 25 mg/kg better than 15 mg/kg. The occurrence of ocular toxicity was also dose-related; >40% of adults developed toxicity at doses of >50 mg/ kg, and 0-3% at a dose of 15 mg/kg/daily. Peak serum EMB concentrations increase in relation to dose, but are significantly lower in children receiving the same dosage. In only 2 of 3811 children (0.05%) receiving EMB doses of 15-30 mg/kg was EMB stopped due to possible ocular toxicity; children of all ages can be given EMB in daily doses of 20 mg/kg (range 15-25 mg/kg) and three times weekly intermittent doses of 30 mg/kg body weight without undue concern.

Tuberculosis immune reconstitution inflammatory syndrome in countries with limited resources.

Abstract: Mycobacterium tuberculosis infection accounts for probably one third of human immunodeficiency virus (HIV) related immune reconstitution inflammatory syndrome (IRIS) events, particularly in developing countries where HIV and tuberculosis (TB) co-infection is very common. Small cohort studies of HIV-positive patients with active TB treated with antiretroviral therapy (ART) suggest an incidence of TB IRIS varying between 11% and 45%. Risk factors for TB IRIS that have been suggested in certain studies but not in others include: starting ART within 6 weeks of starting TB treatment; extra-pulmonary or disseminated disease; a low CD4+ lymphocyte count and a high viral load at the start of ART; and a good immunological and virological response during highly active antiretroviral therapy (HAART). It is important to agree on a clinical case definition of TB IRIS that could be used in resource-limited settings. Such a case definition could be used to determine the exact incidence and consequences of TB IRIS and would be valuable worldwide in clinical trials that are needed to answer questions on how this phenomenon could be prevented and treated.

SLC11A1 (formerly NRAMP1) gene polymorphisms and tuberculosis susceptibility: a meta-analysis.

Abstract: OBJECTIF : Bien que beaucoup d'etudes cas-controle aient investigue les associations entre les polymorphismes du gene SCL11A1 et la sensibilite a la tuberculose (TB), les resultats ont ete discordants par suite du pouvoir statistique limite des etudes. Nous avons revu systematiquement la litterature au cours d'une meta-analyse, fourni une estimation cumulative quantitative sur l'association avec la TB et examine quelques unes des sources d'heterogeneite entre etudes. SCHEMA: Nous avons consulte les bases de donnees (MEDLINE, PUBMED ET OVID) entre janvier 1995 et decembre 2004 en utilisant la combinaison de « gene » ou « SCL11A1 » ou « NRAMP1 » avec « tuberculose » et en outre pratique une recherche manuelle de citations provenant des etudes originales et des articles de revue generale concernes ou encore correspondu avec les auteurs. RESULTATS: Les OR combines pour les etudes sur les variantes des alleles des loci 3'UTR, D543N, INT4 et 5'(GT) dans le gene SLC11A1 ont ete respectivement de 1,33 (IC95% 1,08-1,63), 1,67 (IC95% 1,36-2,05), 1,14 (IC95% 0,96-1,35) et 1,32 (IC95% 1,03-1,68) par comparaison avec les alleles communs correspondants. Les OR combines pour les analyses des sous-groupes pour les quatre loci decrits plus hauts ont ete respectivement de 1,20 (IC95% 0,86-1,68), 1,69 (IC95% 1,14-2,50), 1,50 (IC95% 1,17-1,91), et 1,31 (IC95% 1,05-1,64) chez les sujets d'ascendance africaine, de 1,46 (IC95% 1,10-1,94), 1,65 (IC95% 1,29-2,12), 0,91 (IC95% 0,66-1,25) et 1,86 (IC95% 1,33-2,62) chez les sujets asiatiques, de 1,81 (IC95% 0,66-4,93), 1,79 (IC95% 0,72-4,47), 0,87 (IC95% 0,61-1,22) et 1,02 (IC95% 0,35-2,99) chez les sujets d'origine europeenne. CONCLUSIONS: Les polymorphismes dans les quatre loci ne montrent pas d'association significative entre les variantes de SLC11A1 et la sensibilite a la TB chez les sujets d'ascendance europeenne, mais ils montrent une association statistiquement significative chez les sujets asiatiques (a l'exception de la variante INT4), chez les sujets africains (a l'exception de la variante 3'UTR) et dans l'ensemble de la population etudiee (a l'exception de la variante INT4).

Adherence to anti-tuberculosis chemoprophylaxis and treatment in children.

Abstract: CONTEXTE: Il n'existe que peu de donnees sur l'adhesion au traitement antituberculeux et a la chimioprophylaxie chez les enfants dans des contextes a haute prevalence. OBJECTIF: Determiner l'adhesion a la chimioprophylaxie antituberculeuse et au traitement chez les enfants examines comme contacts au domicile de cas de tuberculose pulmonaire (TBP) de l'adulte. METHODES: Etude retrospective conduite entre janvier 1996 et septembre 2003 dans le Cape Town suburbain en Afrique du Sud ou l'incidence de la TB est elevee. Une recherche de registres a ete faite chez tous les enfants âges de moins de 5 ans identifies comme contacts au domicile de cas de TBP de l'adulte entre 1996 et 2003. On a analyse les donnees sur le depistage de la TB et l'adhesion au traitement prescrit chez les enfants-contact. RESULTATS: On a identifie chez 335 enfants 361 episodes de contact avec 243 cas de TBP chez l'adulte. L'âge median est de 25 mois. L'adhesion au traitement antituberculeux est significativement meilleure que l'adhesion a la chimioprophylaxie (82,6% vs. 44,2% ; OR 6,83 ; IC95% 3,6-12,96). L'adhesion a un regime de chimioprophylaxie de 3 mois a base d'isoniazide et de rifampicine (3HR) est significativement meilleure que l'adhesion a un regime de chimioprophylaxie de 6 mois a base d'isoniazide seule (69,6% vs. 27,6% ; OR 4,97 ; IC95% 2,40-10,36). CONCLUSIONS: Bien que l'adhesion au traitement ait ete bonne, l'adhesion a une chimioprophylaxie non supervisee a ete faible. Nous recommandons que l'on envisage des regimes de chimioprophylaxie courts, tels que 6HR, pour ameliorer l'adhesion. Des etudes complementaires s'imposent.

The global epidemiology of asthma in children.

Abstract: Until recently, most studies reported that asthma prevalence has increased in recent decades. The best indication of what is now happening globally will be provided by Phase III of the International Study of Asthma and Allergies in Childhood (ISAAC) study. Some individual ISAAC centres in Western countries, as well as several studies in adults, have already reported no increase or even a decrease in asthma prevalence over the last 10 years. 'Established' risk factors for asthma cannot account for the global prevalence increases, the international patterns or the recent declines in prevalence in some Western countries. It seems that the 'package' of changes in the intrauterine and infant environment occurring with 'Westernisation' is causing increased susceptibility to the development of asthma and/or allergy. The 'package' includes changes in maternal diet, increased foetal growth, smaller family size, reduced infant infections, increased use of antibiotics and paracetamol and immunisation, all of which have been (inconsistently) associated with an increased risk of childhood asthma, but none of which can alone explain the increases in prevalence. It is likely that the 'package' is more than the sum of its parts, and that these social and environmental changes are all pushing our immune systems in the same direction. To know what that direction is requires that better aetiological theories of asthma are developed to replace the allergen theory, or to incorporate it as a special case. Global comparisons of asthma prevalence and assessment of time trends will continue to play a major role in this process.

Tuberculosis and tuberculosis control in European prisons

Abstract: SUMMARY The Hague, The Netherlands OBJECTIVE: Correctional facilities have often been cited as reservoirs for tuberculosis (TB), presenting a potential threat to the general population. Although correctional facilities are recognised as ideal settings for interventions, little is known about the TB epidemiology within them. The purpose of our survey was to collect data on TB in prisons of the WHO European Region and on existing control measures. DESIGN: A questionnaire was sent to 52 EuroTB correspondents asking for 2002 data on the total number of inmates, number of prisoners with TB, resistance rates, screening strategies, monitoring and responsibilities. RESULTS: Twenty-two (42.3%) countries completed the questionnaire. The median TB notification rate was 232 per 100 000 inmates (0‐17 808). Prisoners had up to 83.6 times more TB than civilians. The majority (90.9%) of the participating countries reported performing active screening for TB on entry into prison, with a median detection rate of 393/100 000 (42‐2362). Of the respondent countries, 81.8% claimed to perform contact investigations and 86.4% to house infectious TB patients separately. CONCLUSION: Although response to this survey was only 42.3% and might be biased by a country’s engagement in TB control in prisons, the results highlight the vulnerability of prisoners to TB and emphasise the need for adequate case-finding and containment strategies in prison.

Poverty and the economic effects of TB in rural China.

Abstract: SUMMARY and Control, Zhengzhou, Henan Province, China OBJECTIVE: To investigate the economic effects of illness on individual tuberculosis (TB) cases in rural China and to use a case-control study to show a strong TB-poverty link. SETTING: In 2002‐2004 we studied 160 new smearpositive pulmonary tuberculosis (PTB) cases and 320 ageand sex-matched controls living in neighbouring houses in four rural counties of Henan Province. DESIGN: Cases and controls were interviewed 1‐3 months after patients were diagnosed. We used matched multivariate logistic regression to compare cases with controls for poverty status using household income, household assets and relative wealth within the village. We conducted follow-up interviews of patients 10‐12 months later to assess economic effects by collecting data on treatment costs, income losses, coping strategies and treatment completion. RESULTS: Poverty is strongly associated with TB incidence even after controlling for smoking and other risk factors. Excluding income losses, direct out-of-pocket treatment costs (medical and non-medical) accounted for 55.5% of average annual household income, and most TB cases fell into heavy debt. The DOTS cure rate was 91%. When DOTS was incomplete or not done, mortality was high. CONCLUSIONS: Poverty is both a cause and a devastating outcome of TB. Ongoing poverty reduction schemes in China must also include reducing TB.

An evaluation of symptom and chest radiographic screening in tuberculosis prevalence surveys.

Abstract: CONTEXTE: En 2002, on a pratique une enquete de prevalence de la tuberculose (TB) dans deux collectivites urbaines a Cape Town, Afrique du Sud. La population etudiee a ete de 36 334 personnes en 2001 et le taux de declaration de TB de 341 nouveaux cas de TB a bacilloscopie positive pour 100000 en 2002. OBJECTIF : Evaluer les contributions relatives du tri par symptomes ou par cliches thoraciques dans la detection de sujets atteints d'une TB a bacilloscopie ou a culture positives dans des enquetes de prevalence. SCHEMA: On a rassemble les informations sur les symptomes, les anomalies des cliches thoraciques (CXR), les resultats des frottis et des cultures dans un echantillon en grappes randomise de 1.170 adultes (≥15 ans). On a utilise comme gold standard la positivite d'un frottis et/ou d'une culture. RESULTATS: Sur 1170 adultes, 29 etaient atteints d'une TB positive a l'examen bacteriologique (positivite du frottis et/ou de la culture). La presence d'une anomalie radiologique quelconque a eu la sensibilite la plus elevee pour la detection de sujets atteints de TB confirmee par l'examen bacteriologique (0,97, IC95% 0,90-1,00). La specificite pour n'importe quelle anomalie du CXR a ete de 0,67 (IC95% 0,64-0,70). La specificite pour n'importe lequel de cinq symptomes lies a la TB etait de 0,68 (IC95% 0,65-0,71). Les sensibilites sont faibles pour les symptomes individuels et d'etendent entre 0,10 pour la fievre et 0,54 pour une toux durant plus de 2 semaines. CONCLUSION: Dans cette enquete de prevalence de la TB, le tri par CXR mais non le tri par symptomes s'est avere une alternative sensible a l'examen des expectorations de l'ensemble des participants.

Treatment outcomes in an integrated civilian and prison MDR-TB treatment program in Russia.

Abstract: CONTEXTE: La tuberculose a germes multiresistants (TB-MR) est un probleme majeur dans les pays de l'ancienne Union Sovietique, a la fois dans le secteur civil et celui des prisons. OBJECTIF: Evaluer les resultats du programme de traitement des TB-MR (DOTS-Plus) a Tomsk, Russie. SCHEMA: Series retrospectives des cas de tous les patients enroles dans ce programme entre le 10 septembre 2000 et le 10 septembre 2002. Le programme implique a la fois les services de TB civils et penitentiaires de Tomsk. On a decrit comme pietres resultats du traitement le deces, l'abandon ou l'echec du traitement. RESULTATS: Sur 244 patients traites, il y a eu 77% de guerisons, 5% de deces, 7% d'echecs et 12% d'abandons. A l'analyse multivariee, les facteurs predictifs les plus marques d'un pietre resultat du traitement ont ete la consommation d'alcool au cours du traitement et la presence de TB a la fois cavitaires et bilaterales. CONCLUSIONS: Dans le programme de traitement de la TB-MR de Tomsk, l'integration des services TB civils et penitentiaires a entraine des taux eleves de guerison et de faibles taux d'abandon. Toutefois, la consommation d'alcool par les patients atteints de TB-MR est associee aux pietres resultats du traitement. Une meilleure comprehension et des interventions du programme en matiere d'alcool sont necessaires si l'on veut qu'un traitement de la TB-MR sur une large echelle soit couronne de succes dans les zones ou les taux d'affections liees a l'alcool sont eleves.

Risk factors associated with default from multidrug-resistant tuberculosis treatment, South Africa, 1999-2001.

Abstract: Multidrug-resistant tuberculosis (MDR-TB) treatment centers in five provinces South Africa. The objectives were to estimate the mortality and evaluate risk factors associated with default from MDR-TB treatment. Using registries and a standardized questionnaire we conducted a case-control study among patients diagnosed and treated for MDR-TB. Cases were defined as patients who began MDR-TB treatment between 1 October 1999 and 30 September 2001 and defaulted from treatment for more than 2 months; controls were defined as patients who began MDR-TB treatment during the same time and were cured completed or failed. After initial identification and reclassification 269 cases and 401 controls were confirmed eligible for interview. Further investigation revealed that 74 (27%) cases and 44 (10%) controls had died. Among 96 cases located who consented and were interviewed 70% had defaulted after receiving at least 6 months of treatment. In a multivariate model the strongest individual risk factors for default included reporting smoking marijuana or mandrax during treatment and having an unsatisfactory opinion about the attitude of health care workers. Mortality among MDR-TB defaulters was high. Interventions to reduce default from MDR-TB treatment should center on substance abuse treatment patient education and support and improving provider-patient relationships. (authors)

Frequency and implications of pyrazinamide resistance in managing previously treated tuberculosis patients.

Abstract: OBJECTIF : Determiner l'etude de la resistance au pyrazinamide (PZA) dans des isolats provenant de patients traites anterieurement a Western Cape, Afrique du Sud. SCHEMA: On a recherche la resistance au PZA par les methodes phenotypiques (BACTEC MGIT 960) et genotypiques (sequencage du gene pncA) sur des isolats cliniques de Mycobacterium tuberculosis resistants a un ou plusieurs medicaments autres que le PZA (la resistance au PZA n'est pas determinee en routine) (n = 127) et sur des cas sensibles aux medicaments (n = 47) provenant de patients traites anterieurement a Western Cape. RESULTATS : Lors de l'analyse MGIT, on a trouve que 68 des 127 isolats resistants aux medicaments etaient resistants au PZA. Presque tous les isolats resistants au PZA (63/68) presentaient diverses modifications des nucleotides dispersees dans le gene pncA et cinq isolats resistants au PZA n'avaient pas de mutations pncA. La sensibilite au PZA existait chez 56 des 57 isolats phenotypiquement sensibles, alors qu'un isolat etait monoresistant au PZA (OR = 53,0 ; IC95% 7,1-396,5). On a egalement mis en evidence un polymorphisme de pncA (Thrll4Met) qui ne transfert pas la resistance au PZA. Il existe une association etroite entre la resistance au PZA et la TB a germes multiresistants (TB-MR). CONCLUSION: Une proportion tres alarmante d'isolats de M. tuberculosis d'Afrique du Sud est resistante au PZA, ce qui suggere qu'on ne doit pas se fier au PZA pour la prise en charge des TB-MR a Western Cape. Une methode pour la detection rapide de la resistance au PZA serait utile pour la prise en charge de patients chez qui une resistance medicamenteuse est suspectee.

Screening for tuberculosis prior to isoniazid preventive therapy among HIV-infected gold miners in South Africa.

Abstract: SETTING: Human immunodeficiency virus (HIV) clinic for employees of a gold mine, Free State, South Africa. OBJECTIVE: To evaluate the process of screening for active tuberculosis (TB) prior to commencing TB preventive therapy in HIV-infected individuals. DESIGN: Cross-sectional study comparing performance of various combinations of screening tests for TB against a gold standard diagnosis of TB based on symptoms, chest radiograph (CXR), sputum microscopy and culture. RESULTS: Of 899 individuals, 44 (4.9%) had TB. The most sensitive symptom combination (59.1%) was any of night sweats, new or worsening cough or reported weight loss; measured weight loss > 5% or abnormal CXR increased sensitivity to 90.9%. Sputum microscopy did not increase sensitivity further, but including World Health Organization HIV clinical staging or CD4 count did. As the specificity of all these combinations was low, many individuals required further investigation to rule out TB. TB prevalence was high (11.7%) among individuals with a CD4 count CONCLUSION: CXR greatly increased the sensitivity of screening for TB in this population. Sputum microscopy conferred no additional benefit among asymptomatic patients with a normal CXR. The high prevalence of TB amongst those with a low CD4 count underlines the importance of screening for active TB prior to commencing TB preventive therapy, and before antiretroviral therapy.

TB in health care workers in KwaZulu-Natal, South Africa.

Abstract: SETTING: Eight public sector hospitals in Ethekwini municipality, KwaZulu-Natal, South Africa. OBJECTIVE: To describe the incidence of TB, clinical presentation and treatment outcomes among health care workers (HCWs) in public sector hospitals in Ethekwini Municipality, KwaZulu-Natal. METHODS: A descriptive study using a retrospective record review for the period January 1999 to June 2004 was conducted from July 2004 to February 2005. RESULTS: Five hundred and eighty three HCWs were diagnosed with TB. The mean incidence of TB among HCWs for the study period was 1133.0 per 100000 HCWs (standard deviation 282.8). The incidence of TB was highest in the age group 25-29 years and among paramedical staff (registered health professionals other than doctors and nurses). Clinical presentation of TB in HCWs included pulmonary TB 76.5% (n = 322) and MDR-TB 3% (n = 13). Cure was achieved in 22.2% (n = 118) of HCWs, and 40.7% (n = 212) of HCWs completed their treatment. CONCLUSION: The incidence of TB in HCWs in KwaZulu-Natal is alarmingly high, and the high incidence in the younger age groups and the poor treatment outcomes are cause for concern. CONTEXTE: Huit hopitaux du secteur public dans la municipalite d'Ethekwini, Kwazulu-Natal, Afrique du Sud. OBJECTIF: Decrire l'incidence de la tuberculose (TB), les signes cliniques et les resultats du traitement chez les travailleurs des soins de sante (HCW) des hopitaux du secteur public de la municipalite d'Ethekwini, KwaZulu-Natal. METHODES: Il s'agit d'une etude descriptive conduite de juillet 2004 a fevrier 2005, utilisant la revision retrospective des dossiers pour la periode de janvier 1999 a juin 2004. RESULTATS: On a diagnostique la TB chez 583 HCW. L'incidence moyenne de la TB parmi les HCW pour la periode d'etude a ete de 1133.0 pour 100000 HCW (deviation standard 282,8). L'incidence de la TB a ete la plus elevee dans le groupe d'âge de 25 a 29 ans ainsi que dans le personnel paramedical (professionnels de la sante enregistres mais autres que medecins et infirmiers). La TB s'est manifestee chez les HCW sous forme de TB pulmonaire chez 76,5% (n = 322) et de TB multiresistante chez 3% (n = 13). On a obtenu la guerison chez 22,2% (n = 118) des HCW et le traitement a pu etre acheve chez 40,7% (n = 212). CONCLUSION: L'incidence elevee de la TB chez les HCW de KwaZulu-Natal est alarmante et l'importance de l'incidence dans les groupes d'âge les plus jeunes et les resultats mediocres du traitement sont inquietants.