Immunonutritional status and pulmonary cavitation in patients with tuberculosis: A revisit with an assessment of neutrophil/lymphocyte ratio.

BACKGROUND: Several reports have described the importance of immunological and nutritional factors in the morbidity and/or mortality of patients with tuberculosis. The aim of this study was to evaluate the association between pulmonary cavitation and immunonutritional status, assessed by parameters such as neutrophil/lymphocyte ratio (NLR) and prognostic nutritional index (PNI), in patients with pulmonary tuberculosis. METHODS: We retrospectively analyzed the data of 137 patients with culture-positive active pulmonary tuberculosis without bacterial pneumonia diagnosed at Kainan Hospital between April 2008 and March 2016. The associations between the levels of serum albumin, lymphocytes, NLR, PNI, platelet to lymphocyte ratio (PLR), and body mass index (BMI) and pulmonary cavitation were evaluated in the patients. RESULTS: A total of 83 men and 63 women (median age, 75 years; range, 16-94 years) were included in the study. Sixty-six patients had smoking history; 55 patients had respiratory symptoms, while 44 patients did not have any symptoms. Patient׳s delay, defined as medical examination performed over 60 days after the onset of symptoms was observed in 25 patients. Univariate analysis showed that high NLR (≥ 5), high PLR (≥200), low serum albumin (<3 g/dL), high neutrophil count (≥6000/mm3), and low lymphocyte count (<1000/mm3) were associated with pulmonary cavitation. Multivariate analysis showed that high NLR and low serum albumin were associated with pulmonary cavitation. CONCLUSION: Malnutrition and increased severity of inflammation may be associated with pulmonary cavitation in patients with tuberculosis. Further studies are warranted to confirm the findings of the present study.

Urine lipoarabinomannan glycan in HIV-negative patients with pulmonary tuberculosis correlates with disease severity.

An accurate urine test for pulmonary tuberculosis (TB), affecting 9.6 million patients worldwide, is critically needed for surveillance and treatment management. Past attempts failed to reliably detect the mycobacterial glycan antigen lipoarabinomannan (LAM), a marker of active TB, in HIV-negative, pulmonary TB-infected patients' urine (85% of 9.6 million patients). We apply a copper complex dye within a hydrogel nanocage that captures LAM with very high affinity, displacing interfering urine proteins. The technology was applied to study pretreatment urine from 48 Peruvian patients, all negative for HIV, with microbiologically confirmed active pulmonary TB. LAM was quantitatively measured in the urine with a sensitivity of >95% and a specificity of >80% (n = 101) in a concentration range of 14 to 2000 picograms per milliliter, as compared to non-TB, healthy and diseased, age-matched controls (evaluated by receiver operating characteristic analysis; area under the curve, 0.95; 95% confidence interval, 0.9005 to 0.9957). Urinary LAM was elevated in patients with a higher mycobacterial burden (n = 42), a higher proportion of weight loss (n = 37), or cough (n = 50). The technology can be configured in a variety of formats to detect a panel of previously undetectable very-low-abundance TB urinary analytes. Eight of nine patients who were smear-negative and culture-positive for TB tested positive for urinary LAM. This technology has broad implications for pulmonary TB screening, transmission control, and treatment management for HIV-negative patients.

Conventional Transbronchial Needle Aspiration: The Original Guard Who Still Has a Role in Mediastinal Lymph Node Sampling.

INTRODUCTION: Conventional transbronchial needle aspiration (C-TBNA) is the originally described method for sampling mediastinal lymph nodes (MLN). After the advent of endobronchial ultrasound, the practice and reports of C-TBNA have dwindled. We report a large series of C-TBNA from the Indian subcontinent, highlighting aspects such as pathological spectrum, yield and complications, and reiterating its relevance in MLN sampling. METHODS: The study population included 400 consecutive patients over 6.8 years who had C-TBNA done for MLN ≥1 cm in size. C-TBNA was done using a 19-G needle, with conscious sedation. A maximum of 7 passes per node were done. Rapid-on-site evaluation was done in >95% cases. Lymph nodes sampled were labeled "adequate" if lymphocytes were present, and "diagnostic" if a definitive diagnosis was made. RESULTS: The study included 228 males and 172 females, mean age 49.4±14.7 years. The "adequacy" rate was 383/400 (95.75%), and "diagnostic" yield was 347/400 (86.75%). C-TBNA was the sole diagnostic modality in 215/400 (53.75%) patients. The diagnoses included tuberculosis (43%), sarcoidosis (25.5%) and malignancy (18.25%). Complications were rare. CONCLUSIONS: This is one of the largest studies of C-TBNA in literature, and one of the few studies to define accurate pathologic diagnosis of enlarged MLN in India. This is also the one of the largest series to define the yield of TBNA with rapid-on-site evaluation in MLN sampling. Currently, in many parts of the world, C-TBNA is still the most common MLN sampling procedure, from an availability, expertise, economic, and safety perspective.

MRI as indicator of pulmonary tuberculosis activity: from morphological to molecular level assessment - a case report.

We present the case of an adult patient with active post-primary pulmonary tuberculosis (TB) and discuss specific morphological and textural aspects found at high-field magnetic resonance imaging (MRI) of the lung. The 42-year-old man, heavy smoker, undertook a routine employment medical examination and was admitted to a referral pulmonology and TB center due to the abnormal findings seen on his chest radiography. The patient presented nonspecific symptoms, bilateral bronchial breath at pulmonary auscultation, inflammatory syndrome on the laboratory blood tests and positive sputum smears for acid-fast bacilli, which together with the typical aspect on the chest radiography lead to a diagnosis of post-primary pulmonary TB and administration of specific medication. To exclude a possible lung cancer and to reevaluate the extent of the disease, computed tomography and magnetic resonance imaging of the lung were performed. The magnetic resonance examination showed, with an accuracy similar to that of computed tomography, the morphology of active post-primary parenchymal TB lesions, as depicted on the T2-weighted acquisition. Moreover, the T1-weighted sequence using iterative decomposition allowed the assessment of both lipid and caseous pneumonia. To the best of our knowledge, this is the first reported case to assess post-primary pulmonary TB using high field MRI equipment, with an analysis from a morphological to a molecular level. By using a fast two-sequence protocol, both morphological, through T2-weighted acquisition, and textural information such as fat content, using dedicated T1-weighted sequence, can be obtained.

Effect of SLCO1B1 Polymorphisms on Rifabutin Pharmacokinetics in African HIV-Infected Patients with Tuberculosis.

Rifabutin, used to treat HIV-infected tuberculosis, shows highly variable drug exposure, complicating dosing. Effects of SLCO1B1 polymorphisms on rifabutin pharmacokinetics were investigated in 35 African HIV-infected tuberculosis patients after multiple doses. Nonlinear mixed-effects modeling found that influential covariates for the pharmacokinetics were weight, sex, and a 30% increased bioavailability among heterozygous carriers of SLCO1B1 rs1104581 (previously associated with low rifampin concentrations). Larger studies are needed to understand the complex interactions of host genetics in HIV-infected tuberculosis patients. (This study has been registered at ClinicalTrials.gov under registration no. NCT00640887.).

Initial assessment of image quality for low-dose PET: evaluation of lesion detectability.

In the context of investigating the potential of low-dose PET imaging for screening applications, we developed methods to assess small lesion detectability as a function of the number of counts in the scan. We present here our methods and preliminary validation using tuberculosis cases. FDG-PET data from seventeen patients presenting diffuse hyper-metabolic lung lesions were selected for the study, to include a wide range of lesion sizes and contrasts. Reduced doses were simulated by randomly discarding events in the PET list mode, and ten realizations at each simulated dose were generated and reconstructed. The data were grouped into 9 categories determined by the number of included true events, from >40 M to <250 k counts. The images reconstructed from the original full statistical set were used to identify lung lesions, and each was, at every simulated dose, quantified by 6 parameters: lesion metabolic volume, lesion-to-background contrast, mean lesion tracer uptake, standard deviation of activity measurements (across realizations), lesion signal-to-noise ratio (SNR), and Hotelling observer SNR. Additionally, a lesion-detection task including 550 images was presented to several experienced image readers for qualitative assessment. Human observer performances were ranked using receiver operating characteristic analysis. The observer results were correlated with the lesion image measurements and used to train mathematical observer models. Absolute sensitivities and specificities of the human observers, as well as the area under the ROC curve, showed clustering and performance similarities among images produced from 5 million or greater counts. The results presented here are from a clinically realistic but highly constrained experiment, and more work is needed to validate these findings with a larger patient population.

Assessment of T cell response to novel Mycobacterium tuberculosis synthetic overlapping peptides mixtures (Rv2659 and Rv2660) and ESAT-6 in Egyptian patients.

Tuberculosis (TB) remains one of the major challenges to the global public health. The most powerful tools in any TB control program are prompt diagnosis and successful treatment of patients with active contagious disease. For almost 100 years the tuberculin skin test (TST) has been used to support the diagnosis of active and latent TB infection. The TST has a number of limitations, most notable low specificity in BCG vaccinated individuals due to cross-reactive components in PPD and the Mycobacterium bovis BCG vaccine strain and an intensive search for new and more specific diagnostic antigens has therefore been ongoing. The current diagnostic techniques utilize production of Interferon-gamma (IFN-γ) in response to novel M. tuberculosis (MTB) synthetic overlapping peptides mixtures to detect MTB infection. The aim of this study was to evaluate human immune responses to two novel Mycobacterium tuberculosis latency associated antigens Rv2659 Pepmix and Rv2660 Pepmix in comparison with ESAT-6 Pepmix. We compared the production of IFN-γ by ELISA following overnight stimulation with the antigens among the different groups of our study, TST negative healthy subjects (n = 16), TST positive healthy subjects (n = 16) and active pulmonary TB patients (n = 30). Our results showed that in TB patients, a positive IFN-γ response was observed to ESAT-6 by 73% of the donors, 47% responded to Rv2659 and 57% responded to Rv2660 when compared to TST negative controls. In conclusion, the ESAT-6 pepmix is recognized in a greater proportion of TB patients compared to Rv2659 and Rv2660, and levels of IFN-γ in response to ESAT-6 are higher than the levels observed in response to Rv2659 and Rv2660.

Delayed diagnosis of sarcoidosis is common in Brazil / Diagnóstico tardio da sarcoidose é comum no Brasil

OBJECTIVE: To determine the frequency of and the factors related to delayed diagnosis of sarcoidosis in Brazil. METHODS: We evaluated patients with a biopsy-proven diagnosis of sarcoidosis, using a questionnaire that addressed the following: time since symptom onset and since the first medical visit; and the number and specialty of the physicians visited. We divided the patients by the timeliness of the diagnosis-timely (< 6 months) and delayed (≥ 6 months)-comparing the two groups in terms of systemic and pulmonary symptoms; extrathoracic involvement; spirometric data; radiological staging; level of education; income; and tuberculosis (diagnosis and treatment). RESULTS: We evaluated 100 patients. The median number of physicians consulted was 3 (range, 1-14). In 11 cases, sarcoidosis was diagnosed at the first visit. In 54, the first physician seen was a general practitioner. The diagnosis of sarcoidosis was timely in 41 patients and delayed in 59. The groups did not differ in terms of gender; race; type of health insurance; level of education; income; respiratory/systemic symptoms; extrathoracic involvement; and radiological staging. In the delayed diagnosis group, FVC was lower (80.3 ± 20.4% vs. 90.5 ± 17.1%; p = 0.010), as was FEV1 (77.3 ± 19.9% vs. 86.4 ± 19.5%; p = 0.024), misdiagnosis with and treatment for tuberculosis (≥ 3 months) also being more common (24% vs. 7%, p = 0.032, and 20% vs. 0%; p = 0.002, respectively). CONCLUSIONS: The diagnosis of sarcoidosis is often delayed, even when the imaging is suggestive of sarcoidosis. Delayed diagnosis is associated with impaired lung function at the time of diagnosis. Many sarcoidosis patients are misdiagnosed with and treated for tuberculosis. .

OBJETIVO: Avaliar a frequência do diagnóstico tardio de sarcoidose no Brasil e os fatores relacionados a esse atraso. MÉTODOS: Avaliamos pacientes com diagnóstico de sarcoidose confirmado por biópsia utilizando um questionário que abordava o tempo entre o início dos sintomas e a data da primeira consulta médica; e o número e especialidades dos médicos consultados. Sintomas sistêmicos e pulmonares, envolvimento extratorácico, dados espirométricos, estadiamento radiológico, escolaridade, renda individual e diagnóstico/tratamento de tuberculose foram comparados entre os pacientes com diagnóstico precoce (< 6 meses até o diagnóstico) e tardio (≥ 6 meses). RESULTADOS: Foram incluídos 100 pacientes. A mediana do número de médicos consultados foi 3 (variação: 1-14). O diagnóstico de sarcoidose foi feito na primeira consulta em 11 casos. Um clínico geral foi inicialmente consultado em 54 casos. O diagnóstico de sarcoidose foi precoce em 41 casos e tardio em 59. Não houve diferença entre os grupos no tocante ao gênero, raça, tipo de seguro saúde, escolaridade, renda, sintomas sistêmicos e respiratórios, envolvimento extratorácico e estadiamento radiológico. Os pacientes com diagnóstico tardio apresentavam menor CVF (80,3 ± 20,4% vs. 90,5 ± 17,1%; p = 0,010) e VEF1 (77,3 ± 19,9% vs. 86,4 ± 19,5%; p = 0,024), além de mais frequentemente receberem diagnóstico de tuberculose (24% vs. 7%; p = 0,032) e tratamento para tuberculose (≥ 3 meses; 20% vs. 0%; p = 0,002). CONCLUSÕES: O diagnóstico de sarcoidose é tardio em muitos casos, mesmo quando há achados de imagem sugestivos. O diagnóstico tardio está associado a menor função pulmonar na época do diagnóstico. Vários ...

Extrapulmonary tuberculosis in the European Union and European Economic Area, 2002 to 2011.

Tuberculosis (TB) is decreasing in the European Union/European Economic Area (EU/EEA), but remains a significant public health problem. Although pulmonary TB accounts for the majority of the cases and is the main transmissible form of the disease, extrapulmonary TB also contributes to the burden of disease and does not receive specific attention in international control strategies. We performed a descriptive analysis to assess the burden and trends of extrapulmonary TB in EU/EEA countries. During 2002­11, 167,652 cases of extrapulmonary TB were reported by the 30 Member States. Extrapulmonary TB accounted for 19.3% of all notified cases, ranging from 5.8% to 44.4% among the Member States. Overall, TB notification rates decreased in 2002­11 due to a decrease in pulmonary TB. Notification rates of extrapulmonary TB remained stable at 3.4 per 100,000 in 2002 and 3.2 per 100,000 in 2011. Thus the proportion of extrapulmonary TB increased from 16.4% in 2002 to 22.4% in 2011. Of all extrapulmonary TB cases reported during 2002­11, 37.9% were foreign-born or citizens of another country, 33.7% were culture-confirmed, and the overall treatment success was 81.4%. A significant percentage of notified TB cases are extrapulmonary, and in contrast to pulmonary TB, extrapulmonary TB rates are not decreasing.

The burden of extrapulmonary and meningitis tuberculosis: an investigation of national surveillance data, Germany, 2002 to 2009.

Tuberculosis (TB) surveillance commonly focuses on pulmonary (PTB) where the main organ affected is the lung. This might lead to underestimate extrapulmonary TB (EPTB) forms, where in addition to the lung other sites are affected by TB. In Germany, TB notification data provide the main site and the secondary site of disease. To gain an overview of all the different EPTB forms, we analysed German TB notification data between 2002 and 2009 using information on both main and secondary disease site to describe all individual EPTB forms. Further, we assessed factors associated with meningitis using multivariable logistic regression. Solely analysing the main site of disease, lead to one third of EPTB manifestations being overlooked. Case characteristics varied substantially across individual extrapulmonary forms. Of 46,349 TB patients, 422 (0.9%) had meningitis as main or secondary site. Of those, 105 (25%) of the 415 with available information had died. Multivariable analysis showed that meningitis was more likely in children younger than five years and between five and nine years-old (odds ratio (OR): 4.90; 95% confidence interval (CI): 3.40­7.07 and OR: 2.65; 95% CI: 1.40­5.00), in females (OR: 1.42; 95% CI: 1.17­1.73), and in those born in the World Health Organization (WHO) regions of south-east Asia (OR: 2.38; 95% CI: 1.66­3.43) and eastern Mediterranean (OR: 1.51; 95% CI: 1.02­2.23). Overall, EPTB manifestations, including meningitis, which is often fatal, were underestimated by routine analysis. We thus recommend using all information on disease manifestation generated by surveillance to monitor severe forms and to transfer the gained knowledge to TB case management where awareness of EPTB is most important.

State of affairs of tuberculosis in prison facilities: a systematic review of screening practices and recommendations for best TB control.

BACKGROUND: Prisoners are at high risk of developing tuberculosis (TB), causing morbidity and mortality. Prison facilities encounter many challenges in TB screening procedures and TB control. This review explores screening practices for detection of TB and describes limitations of TB control in prison facilities worldwide. METHODS: A systematic search of online databases (e.g., PubMed and Embase) and conference abstracts was carried out. Research papers describing screening and diagnostic practices among prisoners were included. A total of 52 articles met the inclusion criteria. A meta-analysis of TB prevalence in prison facilities by screening and diagnostic tools was performed. RESULTS: The most common screening tool was symptom questionnaires (63·5%), mostly reporting presence of cough. Microscopy of sputum with Ziehl-Neelsen staining and solid culture were the most frequently combined diagnostic methods (21·2%). Chest X-ray and tuberculin skin tests were used by 73·1% and 50%, respectively, as either a screening and/or diagnostic tool. Median TB prevalence among prisoners of all included studies was 1,913 cases of TB per 100,000 prisoners (interquartile range [IQR]: 332-3,517). The overall annual median TB incidence was 7·0 cases per 1000 person-years (IQR: 2·7-30·0). Major limitations for successful TB control were inaccuracy of diagnostic algorithms and the lack of adequate laboratory facilities reported by 61·5% of studies. The most frequent recommendation for improving TB control and case detection was to increase screening frequency (73·1%). DISCUSSION: TB screening algorithms differ by income area and should be adapted to local contexts. In order to control TB, prison facilities must improve laboratory capacity and frequent use of effective screening and diagnostic tools. Sustainable political will and funding are critical to achieve this.

Inter-rater agreement in the assessment of abnormal chest X-ray findings for tuberculosis between two Asian countries.

BACKGROUND: Inter-rater agreement in the interpretation of chest X-ray (CXR) films is crucial for clinical and epidemiological studies of tuberculosis. We compared the readings of CXR films used for a survey of tuberculosis between raters from two Asian countries. METHODS: Of the 11,624 people enrolled in a prevalence survey in Hanoi, Viet Nam, in 2003, we studied 258 individuals whose CXR films did not exclude the possibility of active tuberculosis. Follow-up films obtained from accessible individuals in 2006 were also analyzed. Two Japanese and two Vietnamese raters read the CXR films based on a coding system proposed by Den Boon et al. and another system newly developed in this study. Inter-rater agreement was evaluated by kappa statistics. Marginal homogeneity was evaluated by the generalized estimating equation (GEE). RESULTS: CXR findings suspected of tuberculosis differed between the four raters. The frequencies of infiltrates and fibrosis/scarring detected on the films significantly differed between the raters from the two countries (P < 0.0001 and P = 0.0082, respectively, by GEE). The definition of findings such as primary cavity, used in the coding systems also affected the degree of agreement. CONCLUSIONS: CXR findings were inconsistent between the raters with different backgrounds. High inter-rater agreement is a component necessary for an optimal CXR coding system, particularly in international studies. An analysis of reading results and a thorough discussion to achieve a consensus would be necessary to achieve further consistency and high quality of reading.

Current strategies in TB immunotherapy.

Currently available chemotherapy for the treatment of pulmonary tuberculosis (TB) is far from ideal, requiring multiple anti-tuberculous drugs to be taken in combination for extended time periods. This long duration of therapy, coupled with the side effects of current regimens, often results in poor patient adherence, treatment failure and the associated emergence of drug resistance with major financial implications. Thus, the development of novel, shorter treatment regimens is an urgent objective of anti-tuberculous drug discovery. Immunotherapy is an area that merits more consideration than it has previously received, not least, as it could potentially avoid the problem of pathogen resistance. However, this must be undertaken with caution, as at least part of the disease pathology is a consequence of the host immune response. Thus, the protective, and not the harmful, aspects of immunity must be stimulated. Various attempts at utilizing immunotherapy as an adjunct to chemotherapy are reviewed with particular emphasis on the evidence from human studies, including the modulation of cytokine levels, administration of environmental mycobacteria and antibody therapy, in order to modulate or enhance the host immune response to Mycobacterium tuberculosis.

Not all microscopes are equal.

A functional microscope is the most important and most expensive piece of equipment required for smear microscopy. Global Fund monies have provided a unique opportunity to equip laboratories in low-resource countries, but these funds must be spent wisely. Cheap microscopes are superficially appealing. However, higher-quality microscopes generally have better optics and last longer. International agencies should consider establishing a purchasing service to assist countries in their microscope procurement. Such a system would provide quality assurance and increased purchasing power.

Wasting and body composition of adults with pulmonary tuberculosis in relation to HIV-1 coinfection, socioeconomic status, and severity of tuberculosis.

OBJECTIVE: To examine the impact of HIV coinfection, socioeconomic status (SES) and severity of tuberculosis (TB) on the body composition and anthropometric status of adults with pulmonary TB. DESIGN: Cross-sectional study. SETTING: Five TB clinics in Dar es Salaam, Tanzania. SUBJECTS: A total of 2231 adult men and women diagnosed with pulmonary TB, prior to the initiation of anti-TB therapy. METHODS: We compared the distribution of anthropometric characteristics including body mass index (BMI), mid-upper arm circumference (MUAC), triceps skin-fold (TSF), and arm muscle circumference (AMC) by HIV status, SES characteristics, and indicators of TB severity (bacillary density in sputum and Karnofsky performance score). Similar comparisons were carried out with body composition variables from bioelectrical impedance analysis and albumin concentrations, in a subsample of 731 subjects. RESULTS: In multivariate analysis, HIV infection was significantly associated with lower MUAC and AMC in both men and women, but not with BMI or TSF. Compared to HIV-uninfected women, those who were HIV infected had lower body cell mass (BCM) (adjusted difference = -0.85 kg, P = 0.04), intracellular water (-0.68 l, P = 0.04), and phase angle (-0.52, P = 0.02). Albumin concentrations were significantly lower in both men and women infected with HIV. Among HIV-infected men, CD4 cell counts <200/mm(3) were related to lower intracellular water, BCM, fat-free mass and phase angle. Independent of HIV infection, BMI and MUAC were positively related to SES indicators and the Karnofsky performance score; and inversely related to bacillary density. CONCLUSIONS: HIV infection is associated with indicators of low lean body mass in adults with TB; socioeconomic factors and TB severity are important correlates of wasting, independent of HIV. SPONSORSHIP: The National Institute of Allergy and Infectious Diseases (UO1 AI 45441-01).

An assay to compare the infectivity of Mycobacterium tuberculosis isolates based on aerosol infection of guinea pigs and assessment of bacteriology.

The aim of this study was to establish an assay to compare Mycobacterium tuberculosis strains, and cells grown under different growth conditions, in terms of their ability to cause a lung infection and disseminate to the spleen. M. tuberculosis strains H37Rv, Erdman, South Indian (TMC120, SI) and H37Rv cells grown aerobically or under low oxygen/iron limitation in a chemostat were assayed for infectivity. Groups of 8 animals were challenged with 3 different doses of each strain. Lung and spleen bacteriology was assessed at 16 days post-infection for all strains. Bacteriology and lung pathology at day 56 was studied for H37Rv, Erdman and SI. Strains H37Rv and Erdman had a statistically significantly higher pathogenic potential than SI and this was confirmed by analysis of lung pathology performed at 8 weeks post-infection, although the Erdman strain caused more extensive caseation without calcification and little encapsulation. The model could discriminate between cells grown under different growth conditions; low-oxygen/iron-limited cells had a significantly higher infectivity than those grown aerobically. This study presents a quick and reliable method for comparing with statistical confidence, the pathogenic potential of M. tuberculosis strains and the impact of in vitro growth conditions on the infectivity of M. tuberculosis in vivo.

Evaluation of new external quality assessment guidelines involving random blinded rechecking of acid-fast bacilli smears in a pilot project setting in Mexico.

SETTING: Laboratories in Mexico that support the national tuberculosis (TB) control program have been involved in an acid-fast bacilli (AFB) microscopy external quality assurance program which includes rechecking 100% of smears identified as AFB-positive by the local laboratories and 10% of smears identified as AFB-negative. Very few errors have been detected in Mexico using non-random selection and unblinded rechecking of the slides. OBJECTIVE: To evaluate the results from a 1-year pilot program involving blinded rechecking of randomly selected AFB slides from local TB laboratories in two Mexican states and determine its feasibility for future implementation. DESIGN: To reduce potential bias, laboratory staff from the National TB Laboratory, Institute for Epidemiological Diagnosis and Reference (InDRE), performed quarterly statistical sampling of AFB smears and on-site evaluations in local laboratories in each state. AFB smears were rechecked at the respective state laboratories with discordant results resolved at InDRE. RESULTS: A significantly greater percentage of errors was detected on the randomly selected, blinded AFB smears than on the non-randomly selected, unblinded smears. CONCLUSION: Random blinded rechecking provides more accurate estimates of AFB microscopy results, resulting in improved diagnosis and monitoring of treatment response.

Effect of clinical and socio-economic factors on the rate of clustering of Mycobacterium tuberculosis clinical isolates in Elche (Spain).

We studied the association that exists between the epidemiological type clustering of isolates of Mycobacterium tuberculosis and certain clinical, epidemiological and socio-economic characteristics of tuberculosis patients in the Elche health district of Spain. A total of 144 patients diagnosed between 1993 and 1999 and whose isolates had been genotyped by IS6110-RFLP in an earlier study were included. Multivariate analysis showed that the independent variables associated with clustering of strain types were: age (1-25 years, OR 2.92, 95% CI 0.83 10.3), a high percentage of infection in the first circle of contacts (OR 2.89, 95% CI 0.96-8.68), urban dwelling (OR 2.12. 95% CI 0.73-6.2), use of bronchoscopy to obtain samples (OR 16.3, 95% CI 2.3-11.5) and working contact with many people (OR 2.81, 95% CI 0.94-8.3). These data contribute to a better understanding of the epidemiology of tuberculosis and improved systems of control.

Methodology for the assessment of burden of smear-positive pulmonary TB and its infectivity.

OBJECTIVE: The study investigated the burden of smear-positive pulmonary TB and its infectivity using DALY (disability-adjusted life year) as an indicator. METHODS: An assumed cohort of 2,000 cases was set up based on the age-specific incidence of 794 newly registered smear-positive cases in Beijing in 1994. Prognostic trees and model diagrams of infectivity under natural history and DOTS(directly observed treatment, short-course) strategy were established according to the epidemiological evidence. RESULTS: The results showed that 29.6% of DALYs would be neglected if the burden caused by the infectivity was not considered. CONCLUSION: DOTS strategy may reduce 97.3% of the number of potential cases infected, 92.9% of DALYs related to TB-patients themselves, and 99.9% of DALYs caused by TB's infectivity as well.