Chronic respiratory disease in adults treated for tuberculosis in Khartoum, Sudan.

Background: Chronic respiratory disease (CRD) causes substantial morbidity and mortality. Although the global CRD epidemic collides with the tuberculosis (TB) epidemic in many low- and middle-income country settings, the risk of TB-associated CRD is not well described in countries with a high burden of TB. Methods: We recruited 136 patients with a history of sputum smear-positive pulmonary TB (PTB) from the TB clinic at Omdurman Teaching Hospital in Khartoum, Sudan, and 136 age- and sex-matched community controls, between 28 July 2013 and 30 December 2013. Data were collected using standardised questionnaires and spirometry was performed before and after bronchodilator. Results: The mean age of the subjects with previous PTB and controls was respectively 44.0 years (SD 8.5) and 44.5 years (SD 8.6), with 27.2% females in both groups. Chronic respiratory symptoms such as chronic cough (OR 6.67, 95%CI 2.98-14.90, P < 0.001) and the presence of chronic airflow obstruction (OR 12.4, 95%CI 1.56-98.40, P = 0.02) were both strongly associated with a past history of PTB after adjusting for potential confounders. Conclusion: The clinical features of CRDs are strongly associated with past history of PTB. An integrated approach to improve the management of these common conditions should be considered. Contexte : Les maladies respiratoires chroniques (MRC) sont à l'origine d'une morbidité et d'une mortalité considérables dans le monde. Bien que l'épidémie mondiale des MRC entre en conflit avec l'épidémie de tuberculose (TB) dans de nombreux pays à revenu faible ou moyen, le risque de MRC associée à la TB n'est pas bien décrit dans les pays durement frappés par la TB. Méthodes : Nous avons recruté 136 patients ayant des antécédents de tuberculose pulmonaire (TBP) à frottis positif dans le service de pneumologie du Centre Hospitalier Universitaire Omdurman à Khartoum, Soudan, et 136 témoins de la communauté, appariés sur l'âge et le sexe, entre le 28 juillet 2013 et le 30 décembre 2013. Les données ont été recueillies grâce à des questionnaires standardisés ainsi qu'à une spirométrie avant et après bronchodilatateur. Résultats : L'âge moyen des cas et des témoins a été de 44,0 ans (DS 8,5) et 44,5 ans (DS 8,61), respectivement, avec 27,2% de femmes dans les deux groupes. Des symptômes respiratoires chroniques comme une toux chronique (OR 6,67 ; IC95% 2,98-14,90 ; P < 0,001) et la présence d'une obstruction chronique des voies aériennes (OR 12,39 ; IC%95 1,56-98,40 ; P = 0,02) ont été tous deux fortement associés à des antécédents de TBP après ajustement sur les facteurs de confusion potentiels. Conclusion : Les caractéristiques cliniques des MRC sont fortement associées à des antécédents de TBP. Une approche intégrée visant à améliorer la prise en charge de ces pathologies fréquentes devrait être envisagée. Marco de referencia: La enfermedad pulmonar crónica (EPC) es una causa importante de morbilidad y mortalidad. Aunque la epidemia mundial de EPC rivaliza con la epidemia de tuberculosis (TB) en muchos entornos de países con bajos y medianos recursos, el riesgo de aparición de EPC asociado con la TB se ha descrito cabalmente en los países con una alta carga de morbilidad por TB. Métodos: Entre el 28 de julio y el 30 de diciembre del 2013, participaron en el estudio 136 pacientes con antecedente de tuberculosis pulmonar (TBP) y baciloscopia positiva del esputo que habían recibido tratamiento en el consultorio de neumología del Hospital Universitario Omdurman de Jartún, en Sudán, y 136 testigos sanos de la comunidad, emparejados en función de la edad y el sexo. Se recogieron datos mediante cuestionarios normalizados y se practicó una espirometría antes y despuès una prueba de broncodilatación. Resultados: El promedio de la edad en el grupo de los casos fue 44,0 (desviación estándar 8,5 años) y en el grupo de testigos fue 44,5 años (8,6 años); la proporción de mujeres en ambos grupos fue 27,2%. Se observó una fuerte asociación entre la presencia de síntomas respiratorios crónicos como la tos (OR 6,67; IC95% 2,98-14,90; P < 0,001) y la presencia de obstrucción crónica al flujo en las vías respiratorias (OR 12,39; IC95% 1,56-98,40; P = 0,02) en las personas con antecedente de TBP, una vez corregidos los posibles factores de confusión. Conclusión: La presencia de rasgos clínicos de EPC exhibe una fuerte correlación con el antecedente de TBP. Es preciso considerar la posibilidad de aplicar un enfoque integrado con el fin de mejorar la atención de ambas enfermedades tan frecuentes.

Incidence of tuberculosis and associations with indicators of alcohol consumption in three regions of northwest Russia in 1975-2009: a time-series analysis.

BACKGROUND: Alcohol has several social consequences that are associated with increased risk of tuberculosis. However, there have been no studies assessing the links between tuberculosis and alcohol consumption in northwest Russia. The aim of this study was to assess associations between the incidence of tuberculosis and indicators of alcohol consumption in three regions of northwest Russia. METHODS: The study was performed in Arkhangelsk, Murmansk and Vologda regions using the data from 1975 to 2009. Deaths from alcohol poisoning and the incidence of alcohol psychoses were used as indicators of alcohol consumption. Associations between the incidence of tuberculosis and the above mentioned indicators were studied using time-series analysis. RESULTS: We identified significant positive associations between the incidence of tuberculosis and the incidence of alcohol psychoses in the same year in Arkhangelsk region (ß = 0.24, 95% CI: 0.10-0.37) and in Vologda region (ß = 0.18, 95% CI: 0.10-0.25), but not in Murmansk region. CONCLUSIONS: We found an association between the incidence of alcohol psychoses and the incidence of tuberculosis in the same year in Arkhangelsk and Vologda regions suggesting an indirect link between excessive levels of alcohol consumption and the incidence of tuberculosis in Russia.

IgA response to ESAT-6/CFP-10 and Rv2031 antigens varies in patients with culture-confirmed pulmonary tuberculosis, healthy Mycobacterium tuberculosis-infected and non-infected individuals in a tuberculosis endemic setting, Ethiopia.

Little attention has been given to the role of antibodies against Mycobacterium tuberculosis (Mtb) infection. We have compared the levels of IgA and IgG against ESAT-6/CFP-10 and Rv2031c antigens in sera of patients with culture-confirmed pulmonary tuberculosis (PTB), healthy Mtb-infected and non-infected individuals in endemic TB settings. Venous blood samples were collected from 166 study participants; sera were separated and assayed by an enzyme-linked immunosorbent assay (ELISA). QuantiFERON-TB Gold In-Tube (QFTGIT) assay was used for the screening of latent TB infection. The mean optical density (OD) values of IgA against ESAT-6/CFP-10 and Rv2031 were significantly higher in sera of patients with culture-confirmed PTB compared with healthy Mtb-infected and non-infected individuals (P < 0.001). The mean OD values of IgG against ESAT-6/CFP-10 and Rv2031 were also significantly higher in sera of patients with culture-confirmed PTB compared with healthy Mtb-infected and non-infected individuals (P < 0.05). The mean OD values of IgA against both antigens were also higher in sera of healthy Mtb-infected cases compared with non-infected individuals. There were positive correlations (P < 0.05) between the level of IFN-γ induced in QFTGIT assay and the OD values of serum IgA against both antigens in healthy Mtb-infected subjects. This study shows the potential of IgA response against ESAT-6/CFP-10 and Rv2031 antigens in discriminating clinical TB from healthy Mtb-infected and non-infected cases. Nevertheless, further well-designed cohort study is needed to fully realize the full potential of this diagnostic marker.

Prevalence of pulmonary tuberculosis and associated risk factors in Eastern Ethiopian prisons.

OBJECTIVES: To determine the prevalence of pulmonary tuberculosis (PTB) and associated risk factors among inmates in three major prison settings of Eastern Ethiopia. DESIGN: Between July and November, 2008, 371 prisoners with a history of cough of ≥ 2 weeks were screened for PTB using direct smear microscopy and culture. Data were analysed using descriptive statistics and multivariable logistic regression. RESULTS: Of 371 PTB suspects identified by active screening, 33 (8.9%) were confirmed as smear- or culture-positive PTB. Together with the 11 PTB patients already on treatment, the point prevalence of PTB was 1913 per 100,000 (95%CI 1410-2580), about seven times higher than that of the general population. Eleven newly diagnosed PTB patients were sharing a cell with known TB patients. Factors significantly associated with PTB were young age (15-44 years of age) (OR 3.73), urban residence (OR 3.59), having a cough >4 weeks (OR 3.15), and sharing a cell with a TB patient (OR 3.39) or a prisoner with chronic cough (OR 4.5). CONCLUSIONS: The study documented a high prevalence of PTB among Ethiopian prisoners. Socio-demographic and TB management factors were identified to be underlying causes of the high transmission rate and the acquisition of new cases. Active surveillance of TB and implementing prevention and control guidelines are imperative.

Assessment of knowledge and practice about tuberculosis among eastern Ethiopian prisoners.

OBJECTIVE: To assess the level of knowledge and practice related to TB and identify predictive factors in three prisons in eastern Ethiopia: Dire Dawa, Jijiga and Harar. DESIGN: Between July and November 2008, 382 TB patients and suspects were interviewed using a structured questionnaire. Data were analysed using descriptive statistics and ordinal logistic regression. RESULTS: Only six (1.6%) prisoners described the cause of TB as being bacterial, while a wind locally known as 'nefas' was frequently mentioned (36.1%); nearly 75% of the prisoners correctly described breath as a mode of TB transmission; 116 (30.7%) did not know any measures for TB prevention and control; and half of the participants did not know that anti-tuberculosis drugs were provided free of charge. Significant predictors of TB knowledge were: incarceration in the Jijiga (OR 9.62, P < 0.001) and Dire Dawa (OR 2.14, P = 0.016) prisons, those who did not consult and receive treatment for TB symptoms (OR 2.46, P < 0.001), and prisoners without a past history of TB (OR 2.72, P = 0.002). CONCLUSION: The study demonstrates that prisoners have a modest level of biomedical knowledge. As part of the National TB Programme, health education programmes need to be implemented to enhance prisoners' knowledge of TB.

Molecular epidemiology and drug resistance of widespread genotypes of Mycobacterium tuberculosis in northwestern Russia.

SETTING: Four administrative territories (Archangel Oblast, Murmansk Oblast, Republic of Karelia, Republic of Komi) in the northwestern federal region of Russia. OBJECTIVE: To describe the genetic diversity and level of drug resistance in Mycobacterium tuberculosis isolates from new cases of pulmonary tuberculosis. DESIGN: A total of 176 isolates of M. tuberculosis were tested for drug susceptibility and typed with insertion sequence (IS) 6110 restriction fragment length polymorphism (RFLP) and spoligotyping. RESULTS: The Beijing family was found to be the most prevalent (47.1%), most frequently clustered and significantly associated with drug resistance to all first-line anti-tuberculosis drugs (isoniazid, rifampicin, ethambutol, streptomycin and pyrazinamide) and ethionamide, when compared to the T and Haarlem families of M. tuberculosis, which were also prevalent in the study population. Some RFLP clusters (4/10) included isolates that originated from patients residing in different territories, and cases infected with multiple strains of M. tuberculosis were apparently present in the collection. CONCLUSION: The M. tuberculosis population in northwestern Russia appears to be genetically diverse and geographically widespread. Although dominated by isolates assigned to the Beijing family, other families also contribute to the current epidemic, and multiple strain infections may represent a problem in many cases. Extended genetic studies should be encouraged.

Evaluating an active case-finding strategy to identify smear-positive tuberculosis in rural Ethiopia.

OBJECTIVE: To assess an active case-finding strategy for the identification of smear-positive pulmonary tuberculosis (TB) in a rural district of Amhara Region, Ethiopia. METHODS: Study kebeles (smallest administrative units) were randomly selected in a cross-sectional study. House-to-house visits involving individuals aged >or=15 years in all households of the kebeles were conducted. The heads of households were asked to identify subjects with TB symptoms. Identified suspects were asked to provide three sputum samples for smear microscopy. RESULTS: Among the 47,478 individuals living in households that were screened, 1006 TB suspects and 38 cases were detected. This resulted in 38 cases of smear-positive TB, i.e., 80 per 100,000 population, using cluster sampling. The ratio of active vs. passive case detection was 2.5:1, indicating 2.5 undetected TB cases in the community for every smear-positive TB case receiving treatment during the survey period. A higher proportion of female patients was detected by the survey. CONCLUSION: The study revealed a very high proportion of undiagnosed TB. This indicates that the potential for a large infectious pool and significant transmission of TB in the community is high. The expansion of diagnostic facilities and the active involvement of health extension workers is necessary to expedite early detection, timely referral and treatment of TB.

The protective role of antibody responses during Mycobacterium tuberculosis infection.

Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) is one of the most important infectious diseases globally. Immune effector mechanisms that lead to protection or development of clinical disease are not fully known. It is generally accepted that cell-mediated immunity (CMI) plays a pivotal role in controlling Mtb infection, whereas antibody responses are believed to have no protective role. This generalization is based mainly on early classical experiments that lacked standard protocols, and the T helper type 1 (Th1)/Th2 paradigm. According to the Th1/Th2 paradigm Th1 cells protect the host from intracellular pathogens, whereas Th2 cells protect form extracellular pathogens. During the last two decades, the Th1/Th2 paradigm has dominated not only our understanding of immunity to infectious pathogens but also our approach to vaccine design. However, the last few years have seen major discrepancies in this model. Convincing evidence for the protective role of antibodies against several intracellular pathogens has been established. Studies of B cell-deficient mice, severe combined immunodeficiency (SCID) mice, passive immunization using monoclonal (mAb) and polyclonal antibodies and immune responses against specific mycobacterial antigens in experimental animals reveal that, in addition to a significant immunomodulatory effect on CMI, antibodies play an essential protective role against mycobacterial infections. In this review, our current understanding of the essential role of antibodies during Mtb infections, limitations of the Th1/Th2 model and the unfolding interdependence and mutual regulatory relationships between the humoral and CMI will be presented and discussed.

Progress in serodiagnosis of Mycobacterium tuberculosis infection.

One-third of the world population is estimated to have Mycobacterium tuberculosis infection. Accurate and timely identification of infected individuals is critical for treatment and control. The current diagnostic methods lack the desired sensitivity and specificity, require sophisticated equipment and skilled workforce or take weeks to yield results. Diagnosis of extrapulmonary TB, TB-HIV co-infection, childhood TB and sputum smear-negative pulmonary TB pose serious challenges. Interest in developing serodiagnostic methods is increasing because detection of antibody is rapid, simple and relatively inexpensive, and does not require a living cell for detection. Three types of tests, namely screening tests to overcome diagnostic delay, specific tests for diagnosis of extrapulmonary TB and other bacteriologically negative cases, and tests for vaccine-induced immunity need critical consideration. Several factors must be considered to develop serodiagnostic methods for TB. Antigen recognition by infected individuals is highly heterogeneous due to stage of disease, differences in HLA types, strain of the bacilli, health of the patient and bacillary load. With advances in molecular biological techniques, a number of novel antigens have been identified. Some of these antigens have proven valuable in detecting specific antibodies in some of the most challenging TB patients. The best example is a fusion protein containing several M. tuberculosis proteins (e.g. CFP-10, MTB8, MTB48, MTB81 and the 38-kDa protein) which showed encouraging results in detecting antibodies in sera of patients, including TB-HIV co-infection. This review presents progress made in the serodiagnosis of TB during the last decade.

The emergence of Beijing family genotypes of Mycobacterium tuberculosis and low-level protection by bacille Calmette-Guérin (BCG) vaccines: is there a link?

The world is confronted with major tuberculosis (TB) outbreaks at a time when the protection of bacillus Calmette-Guérin (BCG) vaccine has become inconsistent and controversial. Major TB outbreaks are caused by a group of genetically similar strains of Mycobacterium tuberculosis (Mtb) strains, including the Beijing family genotypes. The Beijing family genotypes exhibit important pathogenic features such high virulence, multi-drug resistance and exogenous reinfection. These family strains have developed mechanisms that modulate/suppress immune responses by the host, such as inhibition of apoptosis of infected macrophages, diminished production of interleukin (IL)-2, interferon (IFN)-gamma, tumour necrosis factor (TNF)-alpha and elevated levels of IL-10 and IL-18. They demonstrate distinct expression of proteins, such as several species of alpha-crystallin (a known Mtb virulence factor), but decreased expression of some antigens such as heat shock protein of 65 kDa, phosphate transport subunit S and a 47-kDa protein. In addition, the Beijing family strains specifically produce a highly bioactive lipid (a polyketide synthase)-derived phenolic glycolipid. This altered expression of proteins/glycolipids may be important factors underlying the success of the Beijing family strains. The Beijing family strains are speculated to have originated from South-east Asia, where BCG vaccination has been used for more than 60 years. The hypothesis that mass BCG vaccination may have been a selective factor that favoured genotypic and phenotypic characteristic acquired by the Beijing family strains is discussed.

Cytokine profile during latent and slowly progressive primary tuberculosis: a possible role for interleukin-15 in mediating clinical disease.

Recently, mouse models for latent (LTB) and slowly progressive primary tuberculosis (SPTB) have been established. However, cytokine profiles during the two models are not well established. Using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) we studied the expression levels of interleukin (IL)-2, IL-4, IL-10, IL-12, IL-15, interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha during the course of LTB and SPTB in the lungs and spleens of B6D2F1Bom mice infected with the H37Rv strain of Mycobacterium tuberculosis (Mtb). The results show that, except for IL-4, cytokine expression levels were significantly higher during SPTB than LTB in both the lungs and spleens. During LTB, all the cytokines (except IL-2 in the lungs) had higher expression levels during the initial period of infection both in the lungs and spleens. During SPTB, the expression levels of IL-15 increased significantly from phases 1 to 3 in the lungs. The expression levels of IL-10, IL-12 and IFN-gamma increased significantly from 2 to 3 in the lungs. IL-10 and IL-15 increased significantly from phases 2 to 3, whereas that of TNF-alpha decreased significantly and progressively from phases 1 to 3 in the spleens. Over-expression of proinflammatory cytokines during active disease has been well documented, but factor(s) underlying such over-expression is not known. In the present study, there was a progressive and significant increase in the expression levels of IL-15, together with Th1 cytokines (IL-12 and IFN-gamma) during SPTB but a significant decrease during LTB. IL-15 is known to up-regulate the production of proinflammatory cytokines, IL-1beta, IL-8, IL-12, IL-17, IFN-gamma and TNF-alpha and has an inhibitory effect on activation-induced cell death. IL-15 is known to be involved in many proinflammatory disease states such as rheumatoid arthritis, sarcoidosis, inflammatory bowel diseases, autoimmune diabetes, etc. Our results, together with the above observations, suggest that IL-15 may play an important role in mediating active disease during Mtb infection.

[Impact of drug resistance of the causative agent on the outcomes of treatment for pulmonary tuberculosis in the Arkhangelsk Region].

The present study was undertaken to assess the results of treatment in patients with pulmonary tuberculosis in the Arkhangelsk Region in 1999 and to analyze the results of treatment in relation to the infection with Mycobacterium tuberculosis with different profiles of sensitivity to antituberculous drugs. The outcomes of treatment were assessed in relation to the infection with Mycobacterium tuberculosis with different profiles of sensitivity to antituberculous drugs in 76 patients to whom the BACTEC test was applied. Beneficial effects of therapy were recorded in 150 (63.9%) of the 235 new cases. In 29 (12.3%) patients, it ended in death, ineffective treatment was recorded in 20 (8.5%) first detected patients; 29 (12.3%) new cases discontinued treatment; the result of therapy was unknown in 7 (3.0%). There was a low efficiency of chemotherapy (26.2%), its inefficiency in 24 (39.4%) patients; treatment was discontinued in 18 (29.5%) cases and its outcome was unknown in 1 (1.6%) patient. Resistance to one antituberculous agent timely used in the effective chemotherapy regimen did not affect the outcome of treatment. The spread of drug resistance in pulmonary tuberculosis in the Arkhagelsk Region directly affects the outcome of the disease.

Risk factors associated with typhoid fever in Son La province, northern Vietnam.

Between July and December 2002, we undertook a hospital-based case-control study to identify risk factors associated with typhoid fever in Son La province, northern Vietnam. Among 617 suspected cases, 90 cases of typhoid fever were confirmed by blood or stool culture. One hundred and eighty controls (neighbours of typhoid cases matched for gender and age) were chosen. Participants were interviewed at home using a standardized questionnaire. Seventy-five per cent of cases were aged 10-44 years. No cases in patients aged less than 5 years were recorded in this study. In a conditional logistic regression analysis recent contact with a typhoid patient (OR = 3.3, 95% CI 1.7-6.2, P < 0.001), no education (OR = 2.0, 95% CI 1.0-3.7, P = 0.03) and drinking untreated water (OR = 3.9, 95% CI 2.0-7.5, P < 0.001) were independently associated with typhoid fever. Improving quality of drinking water must be a priority and health education strategies targeted at individuals with no schooling, and contacts of patients, would be expected to decrease the burden of typhoid fever.

Long-term risk of tuberculosis among immigrants in Norway.

BACKGROUND: Two-thirds of the tuberculosis (TB) cases in Norway were discovered among immigrants. Some cases were discovered at arrival, but many develop the disease several years post-migration. Knowledge about how long after migration to Norway TB were discovered will enable us to better target preventive measures including preventive therapy. This study examines the long-term risk of TB among immigrants in Norway. METHODS: All non-Nordic immigrants who arrived in Norway between 1986 and 2002, as registered by the Norwegian Directorate of Immigration, were followed-up. Their TB status was determined from the National Tuberculosis Registry. Observation period for TB cases was calculated from the date of arrival in Norway to TB registration. For persons without TB, it was calculated from the date of arrival in Norway to the date of emigration from Norway, date of death, or until end of follow-up (December 31, 2002). RESULTS: For immigrants from Africa and Asia, the TB rates were 190 and 80 per 100,000 person-years (PY), respectively, at 7 years post-migration. For immigrants from Somalia, Pakistan, Vietnam, and the former Yugoslavia, the rates were 520, 160, 210, and 40 per 100 000 PY respectively, at 7 years post-migration. These rates were 7 to 90 times higher than the crude TB incidence for Norway. This increased risk applies to both genders, pulmonary and extra-pulmonary sites. CONCLUSION: These results indicate the need for health personnel to be aware that immigrants remain at high risk of TB many years post-migration. Screening for TB on arrival should be strengthened, and preventive therapy for those with recent TB infection should be considered.

Resistance of multidrug-resistant strains of Mycobacterium tuberculosis from the Archangel oblast, Russia, to second-line anti-tuberculosis drugs.

Multidrug-resistant tuberculosis has become common all over the world, necessitating the inclusion of second-line drugs in treatment regimens. In the present study, the susceptibility of a selection of multidrug-resistant strains of Mycobacterium tuberculosis isolated in the Archangel oblast, Russia, to second-line anti-tuberculosis drugs was analysed. Susceptibility testing of 77 Mycobacterium tuberculosis strains was performed by the Bactec method using the following recommended drug concentrations: capreomycin 1.25 microg/ml; ethionamide 1.25 microg/ml; kanamycin 5 microg/ml; and ofloxacin 2 microg/ml. The majority of strains (92.2%) were resistant to ethionamide. High rates of drug resistance were also found for capreomycin (42.9%) and kanamycin (41.6%), while nearly all strains (98.7%) were susceptible to ofloxacin. The high rates of resistance to ethionamide, capreomycin, and kanamycin show the real burden of drug resistance in the region and pose a serious problem for the treatment of patients with multidrug-resistant tuberculosis.

Impact of drug-resistant Mycobacterium tuberculosis on treatment outcome of culture-positive cases of tuberculosis in the Archangel oblast, Russia, in 1999.

The objective of this study was to evaluate the outcome of treatment of culture-positive cases of tuberculosis registered in Archangel, Russia, in 1999, and to analyse the influence of Mycobacterium tuberculosis drug resistance on treatment outcome. The outcome of tuberculosis treatment was evaluated for 235 new and 61 previously treated culture-positive cases diagnosed in 1999. Of the 235 new cases, there were 150 (63.8%) cases of treatment completion, 20 (8.5%) cases of treatment failure, 29 (12.3%) cases of death during treatment, and 29 (12.3%) cases in which the patient failed to pick up medications for at least 2 consecutive months. The outcome in 7 (3%) cases was unknown, as the patients were transferred outside the oblast region. Among the 61 previously treated cases, the rate of treatment completion was low (26.2%), and rates of treatment failure (23%) and failure to pick up medications for at least 2 consecutive months (29.5%) were high. The relation between the susceptibility pattern of the infecting strain as determined by the Bactec method and tuberculosis treatment outcome was analysed for 76 patients. The majority (69%) of patients infected with drug-susceptible strains was cured. A large proportion (58.8%) of patients infected with Mycobacterium tuberculosis resistant to more than two drugs did not respond to treatment, i.e. the treatment failed or the patients died. The high rates of death (16.7%) and failure (66.7%) among patients infected with multidrug-resistant strains illustrate the negative impact of multidrug resistance on the outcome of tuberculosis treatment. Pan-resistance was significantly associated with treatment failure (P<0.001). The spread of resistant Mycobacterium tuberculosis has a serious negative impact on the outcome of tuberculosis treatment in Archangel, Russia.

Nasal carriage of Mycobacterium leprae DNA in healthy individuals in Lega Robi village, Ethiopia.

The number of registered leprosy patients world-wide has decreased dramatically after extensive application of WHO recommended Multiple Drug Therapy (MDT). The annual number of new cases has, however, been almost unchanged in several populations, indicating that the infection is still present at community level. Nasal carriage of Mycobacterium leprae DNA was studied in Lega Robi village in Ethiopia. MDT had been applied for more than ten years, and 718 residents over 5 years old were eligible for the study. During the first survey nasal swab samples were collected from 664 (92.5%) individuals. The results of a Peptide Nucleic Acid-ELISA test for M. leprae DNA interpreted by stringent statistical criteria were available for 589 (88.7%) subjects. Thirty-five (5.9%) individuals without clinical signs of leprosy were positive for M. leprae DNA. Seven PCR positive individuals lived in a household where one or two other members were also positive for M. leprae DNA. During a second survey 8 (46%) of 175 interpretable PNA-ELISA tests were positive. Of 137 individuals tested twice, only two were positive on both occasions whereas 10 were PCR positive only once. The study confirms the widespread distribution of M. leprae DNA in healthy individuals. The feasibility of curbing possible transmission of subclinical infection needs further consideration.

Symptoms in patients attending services for diagnosis of pulmonary tuberculosis in Sudan.

OBJECTIVE: To describe the variation in clinical features of individuals presenting to a health facility with chest symptoms according to their ultimate diagnosis. METHODS: Of 16735 patients (52.6% males and 47.4% females) presenting at respiratory centres in seven states in Sudan, 5338 patients were identified with respiratory tract symptoms: 2917 (54.6%) men and 2421 (45.4%) women, with a mean age of 32 years. Those who had cough for more than 3 weeks that was not responsive to a course of antibiotics were screened by microscopy of two or three sputum specimens and chest radiography. RESULTS: A total of 504 (9.44%) were smear-positive, 259 (4.85%) were smear-negative, and 166 (3.11%) had extra-pulmonary tuberculosis, of whom 59 (1.11%) had pleural involvement; the remaining 4409 suspects (82.6%) were non-tuberculous. CONCLUSION: Tuberculosis patients had a constellation of presenting symptoms, with the principal symptom being cough for more than 3 weeks. The accompanying symptoms with greatest predicted significance were weight loss, tiredness and night sweats.

The effect of decentralisation on tuberculosis services in three states of Sudan.

SETTING: Referral hospitals and primary health care (PHC) facilities in Khartoum, Red Sea and Gadaref States. OBJECTIVES: To measure the effect of the decentralisation of the tuberculosis (TB) services on the clinical profile and treatment outcome of tuberculosis. DESIGN: A cohort study of case detection and treatment outcome using information routinely collected comparing patients attending PHC facilities and referral hospitals in selected locations in Sudan. RESULTS: Two-thirds of all TB patients were diagnosed in referral hospitals and one-third in PHC facilities. In PHC facilities, women represented 46% of notified cases, compared to 37.9% in referral hospitals (OR 1.398, 95%CI 1.343-1.455). Older age groups were more likely to prefer PHC facilities to referral hospitals. In referral hospitals, 38% were cured, 29.3% completed treatment without smear examination and 17.3% defaulted, while in PHC facilities 58% were cured, 17.8% completed treatment without smear examination and 11.6% defaulted. CONCLUSION: PHC facilities provide care for a higher proportion of women and older age groups of tuberculosis patients, suggesting a higher level of accessibility for these groups. A higher cure rate and a lower default rate were noted in PHC facilities, possibly reflecting better conditions for directly observed treatment and follow-up.

Tuberculosis in Norway by country of birth, 1986-1999.

OBJECTIVE: To estimate the standardised incidence ratio (SIR) of TB among the foreign-born in Norway. METHOD: The expected number of TB cases was calculated by applying the sex- and age-specific incidence rates for those born in Norway to the corresponding foreign-born population. The SIR was measured as the ratio between observed and expected number of cases. RESULTS: The expected number of TB cases was between zero and three for all selected countries; the observed number of cases was significantly higher. The SIR was highest for Africa (160, 95%CI 144-175) and lowest for USA/Canada (0.4, 95%CI 0.1-1.0). It was 883 for Somalia (95%CI 775-991), 122 for Vietnam (95%CI 106-139), 119 for Pakistan (95%CI 105-134), 115 for the Philippines (95%CI 91-144) and 49 for former Yugoslavia (95%CI 40-57). The SIR for all the foreign-born was 21 (95%CI 20-22), giving a population attributable risk of 38%. It was highest in the age group 15-39 years (95, 95%CI 89-101), and lowest for those 65 years and older (3, 95%CI 2.1-3.3). The SIR for extrapulmonary TB was also high in those aged 15-39 years (159, 95%CI 146-173). CONCLUSION: SIRs for TB differ by country and continent of birth. Understanding local epidemiology and immigration patterns will help better target prevention efforts.