Showing papers in "International Journal of Tuberculosis and Lung Disease in 2002"

A critical review of diagnostic approaches used in the diagnosis of childhood tuberculosis

Abstract: CONTEXTE : Le gold standard du diagnostic de la tuberculose (TB) n'est que rarement obtenu chez les enfants pour qui le diagnostic repose principalement sur les signes cliniques, les symptomes et les investigations speciales. Differentes tentatives en matiere d'approche diagnostique ont ete faites de maniere a rationaliser ce processus de diagnostic. OBJECTIF : Revoir et decrire les publications sur les approches diagnostiques concernant principalement la TB intrathoracique chez les enfants dans les pays en developpement ; comparer les approches diagnostiques entre elles et avec les TB confirmees par l'examen bacteriologique ; decrire les modifications en vue du diagnostic de TB chez les enfants infectes par le VIH ou en etat de malnutrition. METHODES : La revue de la litterature a ete subdivisee en une revue 1) des approches diagnostiques, 2) des caracteristiques utilisees pour les approches diagnostiques et 3) des etudes menees pour valider les approches diagnostiques. RESULTATS : Nous avons analyse 16 systemes. La comparaison entre systemes est difficile car les definitions des caracteristiques et l'ordre de ces caracteristiques ne sont pas standardises ; peu d'etudes scientifiques ont ete menees pour valider ces approches diagnostiques ; dans la plupart des contextes, le gold standard du diagnostic n'est pas utilisable. Seule une minorite de systemes est adaptee aux cas de patients infectes par le VIH ou en etat de malnutrition. RECOMMANDATIONS : Les definitions des caracteristiques et l'ordre de ces caracteristiques devraient etre standardises. Les nouvelles approches diagnostiques elaborees devraient etre adaptees aux pays en developpement et a ressources limitees avec un fardeau eleve de TB, avec malnutrition, VIH/SIDA et une population jeune. Les etudes cherchant a valider les approches diagnostiques devraient etre menees de facon scientifique.

Risk factors associated with default, failure and death among tuberculosis patients treated in a DOTS programme in Tiruvallur District, South India, 2000.

Abstract: OBJECTIVE: To identify risk factors associated with default, failure and death among tuberculosis patients treated in a newly implemented DOTS programme in South India. DESIGN: Analysis of all patients registered from May 1999 through April 2000. A community survey for active tuberculosis was underway in the area; patients identified in the community survey were also treated in this programme. RESULTS: In all, 676 patients were registered during the period of the study. Among new smear-positive patients (n � 295), 74% were cured, 17% defaulted, 5% died and 4% failed treatment. In multivariate analysis (n � 676), higher default rates were associated with irregular treatment (adjusted odds ratio [AOR] 4.3; 95%CI 2.5– 7.4), being male (AOR 3.4; 95%CI 1.5–8.2), history of previous treatment (AOR 2.8; 95%CI 1.6–4.9), alcoholism (AOR 2.2; 95%CI 1.3–3.6), and diagnosis by community survey (AOR 2.1; 95%CI 1.2–3.6). Patients with multidrug-resistant tuberculosis (MDR-TB) were more likely to fail treatment (33% vs. 3%; P � 0.001). More than half of the patients receiving Category II treatment who remained sputum-positive after 3 or 4 months of treatment had MDR-TB, and a large proportion of these patients failed treatment. Higher death rates were independently associated with weight �35 kg (AOR 3.8; 95%CI 1.9–7.8) and history of previous treatment (AOR 3.3; 95%CI 1.5–7.0). CONCLUSIONS: During this first year of DOTS implementation with sub-optimal performance, high rates of default and death were responsible for low cure rates. Male patients and those with alcoholism were at increased risk of default, as were patients identified by community survey. To prevent default, directly observed treatment should be made more convenient for patients. To reduce mortality, the possible role of nutritional interventions should be explored among underweight patients.

Factors associated with patient and health system delays in the diagnosis of tuberculosis in South India

Abstract: OBJECTIVES: To investigate the factors associated with delay in 1) care-seeking (patient delay), and 2) diagnosis by health providers (health system delay), among smearpositive tuberculosis patients, before large-scale DOTS implementation in South India. METHODS: New smear-positive patients were interviewed using a structured questionnaire. RESULTS: Among 531 participants, the median patient, health system and total delays were 20, 23 and 60 days, respectively. Twenty-nine per cent of patients delayed seeking care for �1 month, of whom 40% attributed the delay to their lack of awareness about TB. Men postponed seeking care for longer periods than women (P � 0.07). In multivariate analysis, the patient delay was greater if the patient had initially consulted a government provider (adjusted odds ratio [AOR] 2.2, P � 0.001), resided at a distance �2 km from a health facility (AOR 1.6, P � 0.04), and was an alcoholic (AOR 1.6, P � 0.04). Health system delay was �7 days among 69% of patients. Factors associated with health system delay were: first consultation with a private provider (AOR 4.0, P � 0.001), a shorter duration of cough (AOR 2.6, P � 0.001), alcoholism (P � 0.04) and patient’s residence �2 km from a health facility (AOR 1.8, P � 0.02). The total delay resulted largely from a long patient delay when government providers were consulted first, and a long health system delay when private providers were consulted first. CONCLUSION: Public awareness about chest symptoms and the availability of free diagnostic services should be increased. Government and private physicians should be educated to be aware about the possibility of tuberculosis when examining out-patients. Effective referrals for smear microscopy should be developed between private and public providers.

Pathology and causes of death in a group of 128 predominantly HIV-positive patients in Botswana, 1997-1998.

Abstract: CONTESTE : On connait peu au sujet des causes de deces dans les regions d'Afrique du Sud serieusement atteintes par l'epidemie VIH/SIDA. METHODES : A Francistown, au Botswana, apres avoir obtenu un consentement eclaire, on a realise des autopsies entre juillet 1997 et juin 1998 chez 128 adultes, principalement hospitalises. Pour la selection des cas, les criteres ont inclus les sujets decedes avant l'obtention du diagnostic, ceux dont la condition s'etait deterioree de maniere inattendue pendant l'hospitalisation et ceux qui etaient atteints de maladie respiratoire. Ceci representait en medecine 14% des patients adultes decedes a l'hopital au cours de la periode d'etude. RESULTATS : Sur les 128 patients, 104 (81%) etaient seropositifs pour le virus de l'immunodeficience humaine (VIH). Parmi les patients seropositifs pour le VIH, les conclusions anatomo-pathologiques les plus courantes ont ete la tuberculose (TB) (40%), la pneumonie bacterienne (23%), la pneumonie a Pneumocystis carinii et le sarcome de Kaposi (11%) ; ces conditions etaient la cause de deces chez respectivement 38%, 14%, 11% et 6% des cas. Parmi les 40 cas de TB pulmonaire, 90% etaient egalement atteints d'une TB extrapulmonaire disseminee. Les cliches thoraciques n'ont pas permis de distinguer de facon fiable les pathologies pre-mortem. CONCLUSIONS : Au Botswana, la TB a ete la cause principale de deces parmi nos series d'adultes seropositifs pour le VIH, orientees vers ceux qui etaient atteints d'une maladie pulmonaire ; chez la plupart, elle etait largement disseminee. La pneumonie bacterienne a elle aussi joue un role important dans la mortalite. La pneumonie a P. carinii etait presente mais peu frequente.

Predictors of outcome in patients with tuberculous meningitis.

Abstract: OBJECTIF: Etablir les facteurs predictifs de la mortalite et des sequelles neurologiques chez les patients atteints de meningite tuberculeuse. METHODES: Nous avons evalue les patients atteints de meningite tuberculeuse, traites dans 12 hopitaux universitaires en Turquie entre 1985 et 1997, en utilisant un protocole standardise applique de maniere retrospective. On a determine les variables associees a la mortalite hospitaliere ainsi qu'a la presence de sequelles neurologiques en utilisant des modeles de regression logistique. RESULTATS : On a evalue 434 patients âges de 13 a 83 ans (âge moyen 33 ans). Soixante-huit pour cent de ces patients se situaient aux stades II ou III de la classification du Medical Research Council. Cent et un patients (23,3%) sont decedes et 67 (27%) des survivants evaluables etaient porteurs de sequelles neurologiques. Dans l'analyse multivariee, les convulsions (OR 3,3 ; IC95% 1,2-9,0 ; P = 0,02), l'etat mental comateux (OR 6,0 ; IC95% 3,6-10,2 ; P = 0,01) et le delai ou l'interruption du traitement (OR 5,1 ; IC95% 2,4-11,2 ; P = 0,01) se sont averes des facteurs predictifs de mortalite. La presence de tuberculose extrameningee (OR 2,1 ; IC95% 1,1-4,2 ; P = 0,035), une paralysie des nerfs crâniens (OR 2,6 ; IC95% 1,4-4,2 ; P = 0,01), une hemiparesie ou une faiblesse focale (OR 9,3 ; IC95% 3,8-22,6 ; P = 0,01), une hemiplegie ou des deficits neurologiques multiples (OR 7,1 ; IC95% 2,14-23,38 ; P = 0,01), ainsi que la somnolence (OR 4,2 ; IC95% 2,04-8,82 ; P = 0,01) se sont averes des facteurs predictifs independants de sequelles neurologiques au 6 eme mois apres la sortie de l'hopital. CONCLUSION: Les resultats de cette etude font ressortir l'importance d'un traitement antituberculeux precoce et ininterrompu pour la meningite tuberculeuse. La presence de convulsions ou de coma lors de l'admission a l'hopital sont des facteurs predictifs importants de mortalite alors que la presence de signes neurologiques focaux constitue un facteur predictif de sequelles neurologiques persistantes chez les survivants.

The serum level of soluble urokinase receptor is elevated in tuberculosis patients and predicts mortality during treatment: a community study from Guinea-Bissau

Abstract: OBJECTIVE: To investigate whether the serum level of soluble urokinase plasminogen activator receptor (suPAR) carries prognostic information in individuals infected with Mycobacterium tuberculosis. DESIGN: suPAR was measured by ELISA in 262 individuals at the time of enrolment into a cohort based on suspicion of active tuberculosis and in 101 individuals after 8 months of follow-up. RESULTS: The suPAR levels were elevated in patients with active TB compared to TB-negative individuals (P < 0.001). suPAR levels were highest in patients positive for TB on direct microscopy (n = 84, median suPAR 3.17 ng/ml, P < 0.001), followed by patients negative on direct microscopy but culture positive (n = 35, median suPAR 2.41 ng/ml, P = 0.005) and by patients diagnosed on clinical grounds (n = 63, median suPAR 2.13 ng/ml, P = 0.06) compared to 64 TB-negative individuals (median suPAR 1.73 ng/ml). During the 8-month treatment period, 23 TB cases died. In a multivariate Cox model controlling for HIV status, age, sex, CD4 count and type of TB diagnosis, the mortality increase per ng suPAR was 1.25 (95%CI 1.12-1.40). After treatment, suPAR levels had decreased to the levels of TB-negative individuals. CONCLUSIONS: suPAR levels are elevated in TB patients and associated with mortality. Furthermore, suPAR may be a potential marker of treatment efficacy. (Less)

Defaulting from DOTS and its determinants in three districts of Arsi Zone in Ethiopia.

Abstract: Setting Three districts of Oromia Region in Arzi Zone, Ethiopia. Objectives To determine the rate of defaulting from directly observed treatment, short course (DOTS) for tuberculosis and identify associated factors. Design A case control study. Records of 1367 new tuberculosis patients put on DOTS during a period of 30 months (1 July 1997-31 December 1999) were reviewed to determine the defaulting rate. Cases were defaulters and controls were selected by paired matching of sex and age using the lottery method. All study subjects were actively traced and interviewed by trained interviewers using a pre-tested structured questionnaire. Results The overall rate of defaulting from DOTS was calculated to be 11.3%, while the rate in sputum smear-positive cases was 11.6%. Defaulting was highest (81%) during the continuation phase of treatment. Medication side effects were significantly associated with defaulting (OR = 4.20, 95% CI 1.51-11.66), while adequate knowledge and family support were found to be possible protective factors (OR = 0.04, 95% CI 0.02-0.1 and OR = 0.19, 95% CI 0.08-0.46, respectively). Conclusions Major factors contributing to high rates of defaulting were found to be lack of family support, inadequate knowledge about treatment duration and medication side effects. Control programmes that take these factors into consideration should be successful in reducing defaulting.

Impact of HIV-1 co-infection on presentation and hospital-related mortality in children with culture proven pulmonary tuberculosis in Durban, South Africa.

Abstract: BACKGROUND Diagnosis of tuberculosis (TB) in childhood is difficult and is compounded by HIV-1, as both diseases often co-exist and have many similar features. Most studies from developing countries have included subjects in whom the diagnosis of TB is suspected but not proven. We therefore compare the findings in HIV-infected and non-HIV-infected children with culture-proven TB. METHODS Records were obtained from the laboratory at King Edward VIII Hospital, Durban, South Africa, between January 1998 and December 1999. Children aged 0-12 years with proven pulmonary tuberculosis (sputum, gastric washing or endotracheal aspirate culture for Mycobacterium tuberculosis) from the paediatric medical wards and intensive care unit were included in the study. A retrospective chart review of demographic data, clinical presentation, diagnostic modalities for TB, HIV-1 result, management and outcome were evaluated. RESULTS Of 138 culture-proven cases of TB identified during the study period, the medical records of 118 (86%) could be traced. Of these, 57 (48%) were HIV-1 infected, 44 (37%) non-HIV-1-infected, and in 17 (14%) HIV-1 status was not determined. In contrast to previous studies, this study has shown that TB-HIV co-infection in children is common (48% of all culture-proven cases), the presentation of tuberculosis may be acute (43%), and supportive tests are individually only reliable in confirming a diagnosis in a third of cases. All culture evaluations for M. tuberculosis were positive by 8 weeks. Where other diseases often co-exist with TB and HIV infection and the pressure for hospital in-patient admissions are excessive, the diagnosis of tuberculosis could easily be missed (21.2%). Clubbing and age over 2 years were the most reliable indicators of underlying HIV-1 disease in a child with tuberculosis, while clinical features, radiology and supportive tests were found to be similar between HIV-infected and non-HIV-infected TB cases. Hospital-related mortality, all causes, was higher (17.5%) in the HIV-1-infected than the non-infected group (11.4%). CONCLUSION The changing pattern of presentation of childhood tuberculosis and the high prevalence of TB in HIV endemic areas has made it imperative to maintain a high index of suspicion, with culture evaluation being an important part of clinical practice.

Patients' beliefs: do they affect tuberculosis control? A study in a rural district of South Africa.

Abstract: CADRE : Un district rural d'Afrique du Sud. OBJECTIFS : Decrire les croyances et les experiences concernant la tuberculose chez les patients et les membres de la collectivite et suggerer comment celles-ci pourraient influencer le recours aux services de sante et l'adhesion au traitement. SCHEMA : Etude descriptive utilisant des interviews structurees de patients individualises et des interviews focalisees sur des groupes, soit des groupes de patients, soit des groupes de la collectivite. RESULTATS : Dans cette collectivite, on croit fermement que la tuberculose est le resultat du non-respect des regles culturelles qui exigent l'abstention de rapports sexuels apres la mort d'un membre de la famille et apres qu'une femme ait eu un avortement spontane ou une fausse couche. Les gens croient que la maladie qui en resulte ne peut etre traitee que par les guerisseurs traditionnels. Ceci retarde le recours aux hopitaux ou aux dispensaires. Il existe un type « occidental » de tuberculose qui peut se disperser a partir des malades ou qui est du a une pollution de l'environnement, au tabagisme ou aux abus d'alcool. Un certain nombre de facteurs influencant l'adhesion au traitement ont ete cites; ils incluent la stigmatisation de la tuberculose, l'idee qu'il faudrait s'abstenir de rapports sexuels pendant le traitement, les difficultes d'acces et les longues attentes dans les services de sante, ainsi que des attitudes inacceptables du personnel de sante. CONCLUSIONS: Vu les taux croissants de tuberculose en Afrique du Sud, des mesures serieuses sont necessaires pour mettre en oeuvre un bon programme de lutte susceptible d'augmenter le taux de guerison chez les patients tuberculeux. Les resultats de cette etude suggerent que les travailleurs de sante doivent s'informer au sujet des croyances locales qui peuvent influencer le recours et l'adhesion, et collaborer avec les travailleurs de sante traditionnels.

Hearing loss and nephrotoxicity in long-term aminoglycoside treatment in patients with tuberculosis.

Abstract: OBJECTIVE: To investigate the ototoxic and nephrotoxic effects of long-term use of aminoglycosides. DESIGN: Patients treated for tuberculosis with aminoglycosides were evaluated for hearing loss and nephrotoxicity for a minimum of 14 days. RESULTS: Hearing loss of 15 decibels (dB) at two or more frequencies, or at least 20 dB hearing loss at at least one frequency, was found in 18% of our total population treated with aminoglycosides (amikacin, kanamycin and/or streptomycin). In the group treated with kanamycin this percentage was 15.6. None of the factors sex, age, treatment duration, total aminoglycoside doses or first serum creatinine concentration, was found to be associated with hearing loss. Nephrotoxicity percentages at the end of treatment with aminoglycoside or kana-mycin are 7.5% (1.9%) and 4.5% (2.3%) respectively, using the definition increase of serum creatinine greater than or equal to27 mumol/l (greater than or equal to44 mumol/l). Patients developing nephrotoxicity had a longer duration of treatment and received larger total doses. CONCLUSIONS: Patients developing nephrotoxicity had a significantly longer duration of treatment with aminoglycosides, and received a larger total close. We did not find any factor significantly associated with the development of hearing loss. In the long-term treatment of tuberculosis with aminoglycosides, ototoxicity seems to be a greater problem than nephrotoxicity.

Why do patients with a cough delay seeking care at Lusaka urban health centres? A health systems research approach.

Abstract: SETTING: Primary health centres in urban Lusaka, Zambia. OBJECTIVES: To describe the distribution and risk factors for delay among patients presenting with a cough to the urban health centres. DESIGN: A health systems research methodology was used. A participatory workshop analysed the problem and designed a cross-sectional survey of patients attending two urban health centres. Initial data analyses were performed in a second workshop, with results discussed with a broad range of policy-makers, health care staff and community members interested in tuberculosis. RESULTS: A total of 427 patients were interviewed; 35% had delayed for more than one month. Delay was associated with older age, severe underlying illness, poor perception of the health services, distance from the clinic and prior attendance at a private clinic. There was no relationship between delay and knowledge about tuberculosis, nor with education, socio-economic level or gender. Tuberculosis and HIV were felt to be closely linked and highly stigmatised, but stigmatising attitudes were not associated with longer delays. CONCLUSIONS: The health systems research methodology was an effective way to engage the staff of the district health services in action-oriented research. Investing in improvements in the health system and ensuring accessibility for older and more disabled patients is likely to reduce delays in diagnosis and help to improve tuberculosis control in Lusaka.

Quality assurance programme for drug susceptibility testing of Mycobacterium tuberculosis in the WHO/IUATLD Supranational Reference Laboratory Network: five rounds of proficiency testing, 1994-1998.

Abstract: Setting Quality assurance for the WHO/IUATLD Global Tuberculosis Drug Resistance Surveillance Programme. Objective To implement an ongoing proficiency-testing programme for drug susceptibility testing (DST) of Mycobacterium tuberculosis within the WHO/IUATLD Supranational Reference Laboratories Network (SRLN). Design Five culture panels, each consisting of 10 duplicate drug-susceptible and drug-resistant clinical isolates (100 strains) of M. tuberculosis were tested for resistance to streptomycin (SM), isoniazid (INH), rifampicin (RMP) and ethambutol (EMB). DST procedures included the proportion, absolute concentration and resistance ratio methods, as well as the radiometric BACTEC 460 method. Results The efficiency, sensitivity and specificity of M. tuberculosis DST as well as the intra-laboratory reproducibility showed that the laboratories tested susceptibility to RMP and to INH very reliably, with values ranging from 97% to 99%. The testing of SM and EMB was less dependable, with values ranging from 90% to 95%. The sensitivity of testing of EMB increased from 60% in Round 1 to 98% in Round 5, without a concomitant decrease in specificity. Conclusions This study has shown that regular proficiency testing can significantly improve the quality of DST, even in the most sophisticated TB laboratories. Mean DST efficiency levels of 92% for both SM and EMB and 97% and 99% for INH and RMP, respectively, are proposed as reasonable performance goals for the SRL network. Efficiency, consistently lower than these values, would require remedial action. Efficiency levels lower than mean -1 standard error, i.e., 80% for SM and EMB, 89% for INH and 95% for RMP, should always be considered as sub-standard performance for DST.

Smoking and tuberculosis: an association overlooked.

Abstract: OBJECTIVES This article discusses the role of smoking as a risk factor for tuberculosis. A review of the evidence that has been documented is presented. DATA SOURCES Relevant articles in the medical literature derived from searching the Medline database (1966 to present) with key terms 'smoking' and 'tuberculosis'. The bibliographies of all papers thus located were searched for further relevant articles. RESULTS On searching the database, a total of 12 studies were found. A search of the bibliographies yielded four more articles. Sixteen studies published between 1956 to the present were included in this review. The evidence suggests that smoking could be considered as an important risk factor for the development of tuberculosis. Not only does active smoking appear to heighten the chances of contracting pulmonary tuberculosis, smokers also seem to be at an increased risk for extrapulmonary tuberculosis. Exposure to environmental tobacco smoke in children seems to enhance the hazards of acquiring tuberculosis. Increased tuberculin reactivity, in a dose-dependent manner, was recorded in smokers as compared to non-smokers. CONCLUSIONS Although an association between smoking and tuberculosis appears evident, prospective studies would help to confirm the evidence and to highlight this noxious association. Nevertheless, smoking should be considered as an important risk factor for tuberculosis.

Extra-pulmonary and pulmonary tuberculosis in Hong Kong.

Abstract: Objective To compare the characteristics of patients with pulmonary and extra-pulmonary tuberculosis and to describe the organ involvement, diagnosis and treatment of extra-pulmonary tuberculosis. Materials and methods All patients with a diagnosis of tuberculosis treated by the Hong Kong Government Tuberculosis and Chest Service (Chest Service) in 1996 were studied. Results Of the 5757 patients treated, 13.7% had extra-pulmonary tuberculosis alone and 8.6% had both extra-pulmonary tuberculosis and pulmonary tuberculosis. Extra-pulmonary tuberculosis was more common in women under 30 and over 75 years of age. Only six patients had human immunodeficiency virus (HIV) infection, of whom two had extra-pulmonary tuberculosis. The most common site of extra-pulmonary involvement was the pleura, followed by the lymph nodes. Miliary tuberculosis occurred in only 2.9%. Lymph node involvement occurred significantly higher in women, while pleural disease was significantly higher in men. The duration of treatment varied according to the site of disease, being shorter (6 months) for those with pleural disease only and >9 months for those with miliary, meningeal, gastrointestinal and genitourinary disease; 80.3% completed treatment at 12 months and 85.5% at 24 months. Of those who completed treatment, 1.4% had a relapse of disease at 24 months follow-up; there was no significant difference between those with pulmonary or extra-pulmonary disease. Conclusion In Hong Kong, extra-pulmonary tuberculosis is common, affecting 22.3% of TB patients, and is unrelated to HIV infection. There are sex differences in the organs most commonly affected. The rate of relapse of disease is low for those who completed treatment, irrespective of the site of involvement.

Hemostatic changes in active pulmonary tuberculosis.

Abstract: OBJECTIVE: Severe pulmonary tuberculosis (PTB) is sometimes complicated by deep vein thrombosis (DVT). We have searched for possible hemostatic disturbances that are predisposing factors for venous thrombosis in patients with PTB. DESIGN: Coagulation and platelet function tests were studied in 45 patients with active PTB and 20 healthy control volunteers before therapy. Findings were compared with results at 30 days. RESULTS: Analysis in patients with active PTB showed anemia, leucocytosis, thrombocytosis, elevation in plasma fibrinogen, factor VIII, plasminogen activator inhibitor 1 (PAI-1) with depressed antithrombin III (AT III) and protein C (PC) levels. On the 30th day of treatment, anemia, leucocytosis and thrombocytosis were improved. Fibrinogen and factor VIII levels had decreased to normal levels, PC and AT III levels had increased to normal levels, and there was no difference in PAI-1 levels. We found no activated protein C resistance. Platelet aggregation studies demonstrated increased platelet activation. However, DVT was not detected in patients during the follow-up period. CONCLUSION: Decreased AT III, PC and elevated plasma fibrinogen levels and increased platelet aggregation appear to induce a hypercoagulable state seen in PTB and improve with treatment.

Hepatotoxicity of tuberculosis chemotherapy under general programme conditions in Singapore.

Abstract: Setting The Singapore Tuberculosis (TB) Control Unit, a high volume national referral centre. Objectives To determine the incidence, clinical course and outcome of TB drug-induced hepatitis (DH) and the risk factors associated with DH under general programme conditions. Design A retrospective review of adult patients started on TB treatment in 1998. Results There were 55 cases of DH in the cohort of 1036 patients treated in 1998. The median time to diagnosis of DH was 38 days. Factors significantly associated with DH were abnormal baseline transaminases/ bilirubin (OR 2.1, 95%CI 1.1-4.3, P = 0.02), age >60 years (OR 1.97, 95%CI 1.14-3.34, P = 0.01) and female sex (OR 1.9, 95%CI 1.07-3.4, P = 0.02). Ethnicity, self-reported alcohol consumption and body weight were not associated with development of DH. All three patients with fatal DH had received pyrazinamide-containing regimens. Treatment was re-introduced in 48 patients and successfully completed in 45 patients. The median time to reinstitution of TB treatment was 23 days. Conclusion The incidence of TB drug-induced hepatitis was 5.3%. Age >60 years, abnormal baseline transaminase/bilirubin levels and female sex were risk factors associated with the development of TB drug-induced hepatitis.

What motivates lay volunteers in high burden but resource-limited tuberculosis control programmes? Perceptions from the Northern Cape province, South Africa.

Abstract: SETTING The Northern Cape province, Republic of South Africa. OBJECTIVES To explore factors that motivate lay volunteers to join tuberculosis (TB) control programmes in high burden but resource-limited settings. DESIGN A qualitative study consisting of three focus group discussions and a documentary review of the records of 347 lay volunteers involved in the tuberculosis programme in the Northern Cape province of South Africa. Additional data were also collected in a cross-sectional study that involved questionnaire interviews with 135 lay volunteers. SUBJECTS Lay volunteers in the TB programme. One focus group discussion was also carried out with youth not involved in the TB programme. RESULTS Volunteers do not receive any monetary incentives in the TB programme in the Northern Cape province, but due to the high level of unemployment in this setting, hope for eventual remuneration was found to be the strongest factor motivating youth to join the programme. The study found attrition rates among volunteers to be high (22% had dropped out of the programme within one year of joining); 75% of the dropouts gave loss of interest and a desire for paid work as the reasons for leaving the TB programme. Other motivating factors identified included altruism, a need to find something to do with one's spare time, gaining work experience, and the novelty of the community-based TB programme. CONCLUSION In the absence of monetary incentives, attrition rates of lay volunteers may be high and this can threaten the effectiveness of community-based TB programmes. In resource-limited settings, it is important to identify and implement appropriate alternative incentives that could motivate lay persons in order to sustain community participation in high TB burden areas.

Childhood tuberculosis in Malawi: nationwide case-finding and treatment outcomes.

Abstract: SETTING: All 43 non-private hospitals (three central, 22 [corrected] district and 18 [corrected] mission) in Malawi that register and treat adult and paediatric TB cases. OBJECTIVE: To assess the rate, pattern and treatment outcome of childhood TB case notifications in Malawi in 1998. DESIGN: Retrospective data collection using TB registers, treatment cards and information from health centre registers. Information was collected on number of cases, types of TB and treatment outcomes using standardised definitions. RESULTS: There were 22,982 cases of TB registered in Malawi in 1998, of whom 2,739 (11.9%) were children. Children accounted for 1.3% of all case notifications with smear-positive pulmonary TB (PTB), 21.3% with smear-negative PTB and 15.9% with extra-pulmonary TB (EPTB). Estimated rates of TB in children were 78/ 100,000 in those aged less than one year, 83/100,000 in those aged 1-4 years and 33/100,000 in those aged 5-14 years. A significantly higher proportion of TB cases was diagnosed in central hospitals. Only 45% of children completed treatment. There were high rates of death (17%), default (13%) and unknown treatment outcomes (21%). Treatment outcomes were worse in younger children and in children with smear-negative PTB. Treatment completion was best (76%) and death rates lowest (11%) for the 127 children with smear-positive PTB. CONCLUSION: Childhood TB is common in Malawi and treatment outcomes are poor. Research should be directed towards improved diagnosis and follow-up of children with TB, and the National TB Programme should support appropriate management of childhood contacts of smear positive PTB cases.

Performance of a rapid phage-based test, FASTPlaqueTB, to diagnose pulmonary tuberculosis from sputum specimens in South Africa.

Abstract: CONTEXTE : Douze dispensaires de soins de sante primaire des services administratifs de la Peninsule du Sud, Cape Town, Province du Cap Ouest, Afrique du Sud. OBJECTIF : Evaluer les performances du FASTPlaqueTB, un nouveau test base sur les phages, pour le diagnostic rapide de la tuberculose chez les individus sans antecedents de traitement de la tuberculose, se presentant a des dispensaires de soins de sante primaire a Cape Town, Afrique du Sud. SCHEMA: Etude comparative du test FASTPlaqueTB, de l'examen microscopique des frottis colores a l'auramine et de la culture sur Lowenstein-Jensen pour 1.692 echantillons d'expectoration decontamines provenant de 853 patients suspects de tuberculose. On a entrepris de resoudre les resultats discordants en revoyant les informations cliniques, les cliches thoraciques et le suivi des resultats du traitement. RESULTATS: Le test FASTPlaqueTB a detecte la tuberculose dans 75,2% des cas confirmes par la culture et dans 70,3% de l'ensemble des cas ou le diagnostic clinique de tuberculose a ete porte avec une specificite respectivement de 98,7% et de 99,0%. Les parametres de performance du test FASTPlaqueTB ont ete significativement superieurs a ceux de l'examen microscopique des frottis des expectorations concentrees colores a l'auramine (sensibilite de 63,4% et de 61,3% et specificite de 97,4% et de 97,3% respectivement dans les cas confirmes par la culture et dans l'ensemble des cas). Parmi les patients ayant deux frottis d'expectoration negatifs, le test FASTPlaqueTB a detecte la tuberculose dans 54,1% des cas de tuberculose confirmee par la culture et dans 48,8% de tous les cas ou un diagnostic clinique de tuberculose a ete porte. Une combinaison de l'examen microscopique des frottis et du test FASTPlaqueTB a permis de detecter dans les 2 jours apres leur consultation 81,2% des cas confirmes par la culture et 78,4% de l'ensemble des cas de tuberculose. CONCLUSION: Le FASTPlaqueTB est un test rapide, manuel pour le diagnostic de la tuberculose. Le test a une sensibilite globale significativement plus elevee par comparaison avec la microscopie des frottis d'expectoration colores a l'auramine chez les individus sans antecedents de traitement antituberculeux anterieur; l'examen microscopique des frottis detecte pourtant les plus contagieux des cas de tuberculose. Le test FASTPlaqueTB est aise a pratiquer, ne demande pas un equipement specifique et ses resultats sont lus a l'oeil nu dans les 48 heures. Ce test peut etre utile pour le diagnostic de la tuberculose dans les pays en developpement ou la charge de la tuberculose est importante, la ou d'autres tests rapides de diagnostic peuvent ne pas etre appropries. Le test a des performances prometteuses, particulierement pour le diagnostic des maladies a bacilloscopie negative, et pourrait etre utilise en conjonction avec la microscopie des frottis pour aider au diagnostic de cas supplementaires de tuberculose.

Factors affecting patient compliance with anti-tuberculosis chemotherapy using the directly observed treatment, short-course strategy (DOTS).

Abstract: CADRE : Kota Kinabalu et les collectivites voisines a Sabah en Malaisie. OBJECTIFS : Determiner les facteurs influencant l'adhesion des patients a l'egard d'une chimiotherapie antituberculeuse, leur connaissance de la maladie et leur vision sur l'amelioration du systeme DOTS. SCHEMA : Interviews de patients adherents frequentant les dispensaires pour traitement DOTS et de patients non-adherents a leur domicile entre aout et septembre 2000. RESULTATS: On a interviewe 63 patients adherents et 23 non-adherents. Pour les patients non-adherents, le fait de se rendre au centre de traitement entrainait un cout plus eleve (P < 0,005 ) et un temps de deplacement plus eleve (P < 0,005) par comparaison aux patients adherents. Le cout du transport a ete la raison la plus frequemment citee pour la non-frequentation. Les patients non-adherents etaient plus susceptibles d'avoir termine leur formation secondaire (P < 0,05) et d'etre au travail (P < 0,01). L'atteinte de membres de la famille etait plus frequente chez les patients non-adherents (P < 0,01). On n'a pas observe de difference entre les groupes en ce qui concerne les scores de connaissance de la tuberculose. Toutefois, les patients non-adherents etaient plus susceptibles de penser que le traitement peut etre arrete apres disparition des symptomes (P < 0,01). La plupart des patients (73%) pensent que le systeme DOTS pourrait etre ameliore si l'on fournissait plus d'informations au sujet de la tuberculose. CONCLUSION: L'adhesion a l'egard du DOTS dans la zone de Kota Kinabalu est influencee par les depenses de transport, le temps necessaire pour se rendre dans les centres de traitement et la presence d'une maladie chez d'autres membres de la famille. Les patents souhaiteraient plus d'informations au sujet de la tuberculose.

Risk factors for pulmonary tuberculosis in Estonia.

Abstract: Objective To determine the risk factors for pulmonary tuberculosis incidence in Estonia. Design In a case-control study, the cases were 248 adult tuberculosis patients treated in a hospital in Tallinn between January 1999 and June 2000, and the controls were 248 persons sampled from the Population Registry and matched to cases by sex, year of birth and county of residence. A questionnaire was administered to collect information on potential risk factors. Logistic regression was used to calculate odds ratios and 95% confidence intervals. Results The main risk factors for tuberculosis were marital status other than married, educational level less than higher, low income, having been in prison, not having own place of residence, current unemployment, current smoking, alcohol consumption, shortage of food, and contact with tuberculosis patients. Place of birth was not a risk factor. Risk of tuberculosis decreased for overweight persons whose individual economic situation had improved during the last year. Conclusions The pattern of risk factors for pulmonary tuberculosis in Estonia was somewhat different from that in Western European countries; a large percentage of the patients were men, but were not elderly, and immigration and drug abuse did not increase the risk. Major risk factors were related to poverty and low socio-economic status.

Frequency of recurrence among MDR-tB cases 'successfully' treated with standardised short-course chemotherapy.

Abstract: Setting Ivanovo Oblast, Russian Federation, 300 km north-east of Moscow, where a pilot DOTS TB control programme was implemented in October 1995. Objective To determine the frequency of TB recurrence among MDR (multidrug-resistant) patients who achieved treatment 'success' on standard short-course chemotherapy. Methods All patients with MDR tuberculosis, defined as resistance to at least isoniazid and rifampicin, who were declared 'cured' or 'treatment completed', were identified using the district register and traced whenever possible. Eligible patients underwent medical examination and, if necessary, chest radiography, sputum smear examination, culture and susceptibility testing. If the patient had died, the relatives were interviewed to try to determine the reasons for death. Results Of 18 patients eligible for analysis, five (27.8%) were documented to have recurrence (two of seven patients resistant to HRSE, one of five patients resistant to HRS and two of six patients resistant to HR). Patients receiving the Category I regimen were more likely to relapse than those receiving the Category II regimen (40% vs. 12.5%). The median time to relapse was 8 months; 2.46 recurrences were observed in 100 person-months (3.17 in category I and 1.3 in Category II patients). Conclusions The frequency of TB recurrence among MDR-TB patients declared 'cured' after short-course chemotherapy is high. Improvements in treatment success, after removal of programme-related pitfalls in the treatment delivery process, must incorporate methods for early detection of MDR, along with adequate treatment regimens including second-line drugs. Culture-based bacteriological confirmation at the end of treatment is recommended.

Low plasma concentrations of rifampicin in tuberculosis patients in Indonesia.

Abstract: SETTING: Although rifampicin is a key drug in tuberculosis treatment, little is known about its quality and bioavailability in countries endemic for tuberculosis. High drug levels may lead to increased toxicity, while low drug levels may predispose to treatment failure and relapse. OBJECTIVE: To investigate possible variations in the bioavailability of plasma rifampicin in tuberculosis patients in Indonesia. DESIGN: Plasma concentrations of rifampicin and the rifampicin content of drug formulations in use were measured among 62 non-selected tuberculosis patients in Jakarta, Indonesia. RESULTS: Plasma concentrations of rifampin were generally low: 70% of patients had 2-hour plasma concentrations (Cmax) below 4 mg/L. No toxic plasma concentrations of rifampicin (>20 mg/L) were found. The strongest predictive factor for the magnitude of rifampicin concentrations was the drug manufacturer. The rifampicin content of the different drug preparations used was normal (90.5-103.6% of the reference standard). No association was found between low plasma rifampicin concentrations and delayed sputum conversion or treatment failure. CONCLUSION: The unexpectedly low plasma concentrations of rifampicin in this setting are most likely due to reduced bioavailability of local drug preparations, as the rifampicin content of the drug preparations was found to be normal. The clinical significance of these findings remains to be determined.

Smoking in Syria: profile of a developing Arab country.

Abstract: One of the main obstacles to tobacco control in the Middle East lies in the shortage of reliable standardised data on the spread and patterns of tobacco use in society. In Syria a project aiming at drawing an epidemiological map of the tobacco epidemic in this country was started 4 years ago. Overall nine studies have resulted with a total of 6780 participants. The crude prevalence of current smoking among adults in Syria based on combined information from all studies is 48% and 9% for males and females respectively. The prevalence of current smoking among high school adolescents is 16% and 7% for boys and girls respectively and was strongly associated with parental and sibling smoking. High school students from families with parents and/or siblings who smoked were 4.4 times more likely to be current smokers than those from non-smoking families. The biggest influx of new smokers among males in Syria is occurring in the early twenties but an earlier pattern can occur among youths with low academic performance or socioeconomic status. Smoking in women evaluated by data from physicians tends to start later than in men and continues to increase with age. Womens smoking in Syria is related to their level of social liberalisation. Data show that active smoking is associated with an increased risk of respiratory diseases among smokers and that exposure to environmental tobacco smoke (ETS) is associated with an increased risk of respiratory symptoms in children. Knowledge about the harmful effects of smoking and the desire to quit are disproportionate to the rate of successful cessation. The evidence collected indicates possible avenues for tobacco control in Syria including price increases smoking cessation programmes restriction of adolescents access to cigarettes and intensive prevention work among women. (authors)

Rapid and simple MTT method for rifampicin and isoniazid susceptibility testing of Mycobacterium tuberculosis.

Abstract: The MTT method for rifampicin and isoniazid susceptibility testing of Mycobacterium tuberculosis was developed by using bacterial suspension prepared from colonies on solid media. The MTT tube assay in 1 ml Middlebrook 7H9 broth was completed within 4 days for rifampicin (RMP) and within 7 days for isoniazid (INH). When MTT assay results with 279 M. tuberculosis clinical isolates were compared with those of the conventional proportion method on Lowenstein-Jensen medium, high specificity and sensitivity values of 100% and 94.1%, respectively, for RMP susceptibility testing, and 99.5% and 89.2%, respectively, for INH susceptibility testing were obtained. The accuracy of the MTT method for RMP and INH was > 0.97 concordance with the proportion method. The MTT method is simple, inexpensive and rapid. The high level of agreement with the conventional proportion method suggests a potential to rapidly detect drug-resistant M. tuberculosis in developing countries, as only basic microbiological equipment is need.

Circulation level of matrix metalloproteinase-9 is correlated with disease severity in tuberculosis patients.

Abstract: SETTING Parenchymal lung destruction accompanied by active tuberculosis is, at least in part, caused by host as well as bacillus metalloproteinases. Mycobacterium tuberculosis has been shown to stimulate MMP-9 expression in the lung of infected organisms. DESIGN We have used quantitative zymography and computer-assisted image analysis to measure the levels of type IV collagenases in 20 serum samples of patients with active tuberculosis and in 23 serum samples of healthy volunteers. RESULTS Mean levels of the serum MMP-9 were over three-fold higher in tuberculous samples compared with normal serum (P < 0.0001), whereas the MMP-2 levels did not differ in these two groups. The levels of MMP-9 were significantly higher in subjects with advanced disease than in those with only limited disease changes (P < 0.05). CONCLUSIONS We suppose that the elevation of serum MMP-9 levels in patients with tuberculosis is affected by the augmentation of synthesis and/or secretion of this enzyme by inflammatory cells in response to M. tuberculosis infection. The observed association between the serum MMP-9 level and the extent of radiological change suggests that the quantification of the serum level of this enzyme may constitute a supplementary test in pulmonary tuberculosis diagnostics.

Optimal tuberculosis case detection by direct sputum smear microscopy: how much better is more?

Abstract: CADRE : Un projet de lutte antituberculeuse au Bangladesh. OBJECTIF : Definir l'efficience du nombre de champs microscopiques examines et celle du schema du recueil des expectorations utilise pour l'examen des frottis pour diagnostic. SCHEMA: Des controleurs de qualite ont pris note des nombres cumulatifs de BAAR par 100 champs examines. Le rendement supplementaire de diagnostic de differentes strategies d'echantillonnage des expectorations a ete determine. Les series douteuses ont ete recontrolees et/ou d'autres echantillons ont ete examines. RESULTATS: On a decele des BAAR dans les 100 premiers champs chez 99,6% de 1.412 frottis positifs et dans 79,3% de 576 lames contenant de rares bacilles. L'examen d'un troisieme echantillon a fourni au maximum un rendement supplementaire de 2,7% de positifs. La strategie la plus efficace utilisant trois echantillons du matin a obtenu 94,2% de positifs sur le premier et 1,0% sur le troisieme echantillon. Bien que 10% des suspects ne soient pas revenus, 1,5% seulement des positifs se retrouvaient parmi eux et un nombre plus grand de cas ont ete confirmes et traites. La valeur predictive positive d'un frottis unique positif ou contenant de rares bacilles est tres elevee (99,2%). CONCLUSIONS: La lecture de plus de 100 champs par frottis ou l'examen d'une troisieme expectoration ont un rendement insuffisant pour justifier la charge de travail. L'examen des seules expectorations du matin est plus efficient et leur recueil n'entraine pas necessairement d'inconvenients pour les patients. Le traitement peut demarrer sur la base d'un frottis positif. Pour autant qu'un systeme performant de controle de qualite de la bacilloscopie soit en place, nous proposons une strategie basee sur l'examen de deux expectorations matinales pour les suspects negatifs et sur un diagnostic reposant sur un seul resultat positif.

A retrospective study for the outcome of pulmonary resection in 49 patients with multidrug-resistant tuberculosis.

Abstract: BACKGROUND Outcome of treatment using only chemotherapy for multidrug-resistant tuberculosis is usually considered not to be satisfactory. The combination of chemotherapy with surgical treatment has been producing higher acid-fast bacilli (AFB) negative sputum conversion and longer survival rates. This treatment strategy may be the solution for patients with multidrug-resistant tuberculosis. MATERIALS AND METHODS A retrospective review was performed of the medical records and laboratory findings of 49 patients with multidrug-resistant tuberculosis among 130 patients who underwent pulmonary resection for pulmonary tuberculosis between January 1995 and December 1999 at National Masan Tuberculosis Hospital, Korea. RESULTS The mean number of drugs to which the patients were resistant was 4.5. Patients had a mean age of 35 years. Cavitary lesions on plain chest X-ray were shown in 43/49 patients (87.8%); 31 had positive sputum cultures preoperatively (63.3%). The surgical techniques used were as follows: 12 pneumonectomies, 28 lobectomies, seven lobectomies with segmentectomies or wedge resections, one wedge resection and one cavernoplasty. The AFB negative sputum conversion rate was 93.5% with continuous postoperative chemotherapy. There were no deaths after surgery. Postoperative complications that developed were six cases of air leakage over a week, one of postoperative bleeding and one of wound infection. CONCLUSIONS This study demonstrated the effectiveness of pulmonary resection with postoperative chemotherapy in cases of multidrug-resistant tuberculosis. Although there are different ideas about indications for surgery and the length and content of postoperative drug regimens, pulmonary resection should be considered an effective measure in combination with chemotherapy for treatment of multidrug-resistant pulmonary tuberculosis.

Variations in the NRAMP1 gene and susceptibility of tuberculosis in Taiwanese.

Abstract: CADRE: Hopital Universitaire National de Taiwan, Taipei, Taiwan. OBJECTIF : Etudier les variations du gene NRAMP1 par l'utilisation de cinq genotypes [274C/T, 577-18G/A, A318V, D543N I et la region 3' non-transferee (UTR)], et leur association avec une predisposition a la tuberculose et a l'infection VIH chez les Taiwanais. SCHEMA: L'echantillon etudie comporte 49 patients atteints de tuberculose, 48 sujets-controle bien portants et 68 patients infectes par le VIH. Les produits amplifies par PCR a partir de leur DNA genomique ont ete soumis a une digestion par les enzymes de restriction et analyses par electrophorese sur gel d'agar. RESULTATS: A318V n'est pas polymorphique dans la population etudiee. Seuls D543N et 3'UTR etaient plus heterozygotes. Pour 274C/T et 577-18G/A, les frequences des alleles montrent que le type predominant presente une allure homozygote C/C (94%) et G/G (94%), respectivement. Il n'y a pas eu de differences significatives entre les patients tuberculeux et les sujets-controle sains. Malgre la forte predisposition a la tuberculose chez les patients infectes par le VIH, les frequences des genotypes chez les patients infectes par le VIH ne sont pas significativement differentes entre les patients tuberculeux (n = 29) et les non-tuberculeux (n = 31). Par comparaison avec des etudes anterieures, il n'y a pas de differences significatives dans les divers groupes ethniques en ce qui concerne les frequences des alleles pour 274C/T, D543N et 3'UTR. CONCLUSION: Le polymorphisme de l'allele et du genotype de NRAMP1 parmi les Taiwanais differe de ceux des Caucasiens, des Africains et des Hispaniques. On n'a pas pu identifier d'associations d'alleles entre les alleles NRAMP1 et la predisposition a la tuberculose.