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[The usefulness of adenosine deaminase determination in biological fluids for tuberculosis diagnosis].

Tuberculosis may affect several organs and its prevalence is continuously increasing. Laboratory diagnosis still remains difficult. Adenosine deaminase (Ada) is an enzyme which contributes to purine metabolism and its presence in lymphocyte, monocyte and macrophage cells is associated with T cells mediated immunity. Many studies have shown the usefulness of Ada determination in various biological fluids for the diagnosis of tuberculosis. In pleural fluid, cutoff vary from 33 to 48 U/L, with sensitivity higher than 80% and specificity near 100%. In peritoneal fluid the cutoff value is 30 U/L. In cerebrospinal fluid, the value of 7 U/L can make discriminate negative and positive cases with a good sensitivity and specificity. The data from the literature show that 50 U/L in pericardic fluid is a reliable threshold for tuberculosis diagnosis. Ada determination in serum is not as relevant as in others fluids because of its low specificity. Ada measurement in biological fluids, easy and not expensive, may be add to other biological tests for tuberculosis diagnosis.

Adenosine Deaminase↗

Delayed tuberculosis diagnosis and tuberculosis transmission.

SETTING: Tuberculosis (TB) patients and their close contacts reported to the Maryland Department of Health and Mental Hygiene from 1 June 2000 to 30 November 2001. OBJECTIVES: A recent prospective study found that 49% of pulmonary TB patients had total treatment delays > or = 90 days. This cohort was analyzed to determine the association between total treatment delay and TB transmission. DESIGN: TB patient data were collected as part of a prospective cohort study; contact data were collected from local health departments. RESULTS: Close contacts of 54 US-born patients (n = 310) and those of 70 foreign-born cases (n = 393) received tuberculin skin tests (TSTs). Among contacts of US-born patients with a total treatment delay of > or = 90 days, 40% had positive TSTs vs. 24% contacts of patients with shorter delays (aOR 2.34; P = 0.03). Other patient factors associated with TST positivity among contacts of US-born cases were black race (aOR 3.03; P = 0.05), sputum smear positive for AFB (aOR 3.29; P = 0.01) and chest radiograph with cavitation (aOR 3.11; P = 0.01). No associations were observed between foreign-born patients and risk of TST positivity among their contacts. CONCLUSION: Among US-born patients, delay in TB diagnosis is associated with greater transmission of infection to contacts and could be used independently of other index patient factors to identify contacts at greatest risk of TB infection.

Contact Tracing↗

[Various approaches to tuberculosis diagnosis in patients with hemoblastosis].

AIM: To characterize diagnosis of tuberculosis in hemoblastosis patients. MATERIAL AND METHODS: Diagnosis of active tuberculosis in 2.6% from 2123 hemoblastosis patients admitted to Hematological Research Center in 1990-1999 shows that such patients can be referred to high risk group in relation to tuberculosis infection. Methods and terms of tuberculosis diagnosis in hemoblastosis patients are analysed. RESULTS: Bacteriological and histological tests were positive in 27.8% examinees with hemoblastosis. In extrapulmonary tuberculosis location, histological diagnosis was positive in 60%. Especially helpful is a complex of clinical and x-ray examinations in high tuberculosis alertness. This allowed to suspect the infection in 51.9% patients (63.9% had pulmonary location). A marked positive response to antituberculosis treatment proved tuberculosis diagnosis. CONCLUSION: Difficulties of tuberculosis diagnosis in hemoblastosis patients are explained by low informative effectiveness of most common methods of this infection verification. Therefore, in addition to bacteriological and histological examinations, clinical diagnostic techniques should be employed keeping alert in relation of tuberculosis in hemoblastosis patients who are at risk to catch this infection.

Acute Disease↗

[Sources of errors and pitfalls in tuberculosis diagnosis].

Three cases of tuberculosis infection are presented (spondylitis, meningitis, pericarditis). Pitfalls and blunders delaying tuberculosis diagnosis are reported. The authors emphasize that: Children at risk have to be vaccinated with BCG (1.1). Health professionals must repeatedly be taught in the interpretation of tuberculin test results and chest X-rays. Tuberculous meningitis may be hidden by the presentation of only encephalitis symptoms and liquor analysis reveals an atypical result (3). Spontaneous resolution of the symptoms or an improvement under non-tuberculostatic therapy does not exclude tuberculosis. In fact encephalitic signs may improve or disappear spontaneously despite subsequent positive liquor culture (4).

Adolescent↗

[Usefulness of antibodies against A60 mycobacterial antigen in tuberculosis diagnosis].

Diagnosis of tuberculosis is based on clinico-radiological symptoms and on identification of mycobacteria. Accuracy of both methods is limited. Therefore reliable serologic test would have considerable advantage. The goal of our study was to evaluate serologic response against A60 mycobacterial antigen in group of 270 patients (pts) (137 pts with active tuberculosis (TB), 15 pts with mycobacterial infections other than TB (MOTT), 58 pts with sarcoidosis, 26 pts with lung cancer and 34 healthy controls. We used commercially available ELISA based kits against antigen A60 (ANDA-TB). Specificity of 87% for IgG, of 94% for IgA and for IgM, of 85% for IgG + IgA, of 89% for IgA + IgM, of 80% for IgG + IgM, and of 79% for IgG + IgA + IgM was achieved. Sensitivity of 40% for IgG, of 30% for IgA, of 18% for IgM, of 56% for IgG + IgA, of 35% for IgM + IgA, of 50% for IgG + IgM, and of 59% for IgG + IgA + IgM was obtained. The results demonstrated that humoral response differs depends on the immunoglobulin class. Measurements of IgG or IgG and IgA as most sensitive against A60 are potentially more useful serological tests in clinical practice. It is not recommended to use tests based on antigen A60 for differentiation tuberculosis and MOTT.

Antigens, Bacterial↗

Evaluation of two novel Ziehl-Neelsen methods for tuberculosis diagnosis.

BACKGROUND: Currently, the diagnosis of tuberculosis (TB) in Ghana relies on direct sputum smear, Ziehl- Neelsen (ZN) staining method. This method has low sensitivity and poses some health risks. The study was to compare the, direct sputum smear, (ZN) staining method against two newer ZN methods; 1% Sodium hypochlorite (NaOCL)-xylene floatation and 1% NaOCL sedimentation methods, to determine the most sensitive and the safest STUDY DESIGN: A prospective descriptive study involving 150 adult patients attending Komfo Anokye Teaching Hospital, Kumasi, Ghana suspected of pulmonary tuberculosis, using the three ZN microscopy methods: direct sputum smear, 1% NaOCL sedimentation, and 1% NaOCL-xylene floatation, for the detection of acid fast bacilli (AFB). Sputum culture on Lowenstein-Jensen (LJ) slopes was used as the gold standard for determining the sensitivity and specificity rates. RESULTS: The sensitivity rates of NaOCL sedimentation, NaOCL-xylene floatation and direct smear methods were 77.2%, 71.8% and 66.3% respectively. The specificity rate was 95.9 % for all three methods. Whereas the difference between the NaOCL sedimentation and the direct smear methods was statistically significant (P= 0.0446), that between the NaOCL-xylene floatation and direct smear was not (P=0.1788). CONCLUSION: In spite of the cost of chemicals, the hypochlorite sedimentation method was found to be the most accurate and the safest.

Adult↗

[Development of a multiantigenic serological test for tuberculosis diagnosis].

OBJECTIVE: The present work evaluated a multi-antigen printing immunoassay (MAPIA) for the serological diagnosis of tuberculosis. MATERIALS AND METHODS: Sera were obtained from 66 patients with tuberculosis, verified clinically and bacteriologically and from 47 healthy individuals (control group). Sample sera were used for detection of antibodies against 3 enriched mixtures of proteins and 5 unique recombinant antigens. The antigens were presented in a solid matrix. Sensitivity, specificity and predictive values were evaluated and confirmed by a logistic regression analysis. A prevalence value was calculated and used for the selection of the best antigenic combination. RESULTS: The sensitivity and specificity values of individual antigens varied between 5-83% and 9-100%. The enriched mixtures values were more accurate than those obtained with the recombinant antigens. Combinations of several antigens improved the sensitivity values up to the 81% level. In most cases, specificity values of 57% or less were obtained. CONCLUSIONS: These results suggested that the multiantigenic test can be a useful screening tool, to be used in conjunction with the more definitive diagnostic tests.

Antibodies, Bacterial↗

[Study on factors causing the delay of access to tuberculosis diagnosis and its influencing factors in migrating tuberculosis patients in Putuo district, Shanghai].

OBJECTIVE: To describe factors causing the delay of diagnosis among non-resident tuberculosis (TB) patients and to study its implications from demographic, socio-economic aspects in order to provide information to policy makers for TB control programs in Shanghai. METHODS: A historical cohort study through questionnaire interview was conducted in 146 newly diagnosed TB patients. The questionnaire covered the general information of subjects and information on patients' health care seeking experiences from the first symptom to the TB diagnosis in health facilities. Index adopted to reflect the access to TB diagnosis would include the days due to delayed diagnosis consisting the days from both patient's and doctor's responsibilities. RESULTS: The median days due to patients' delay was 19 (7-33.5) days, which was 3.8 times longer than 5 (2.5-10) days caused by doctor's. The median of total diagnostic delay was 31 (11-59) days. Female TB patients, patients with lower than annual 5000 Yuan income had an increased risk of a longer diagnostic delay with an OR of 3.226 and 11.958 relatively. Smear positive patients had a shorter delay (OR = 0.280, P < 0.05). CONCLUSION: Delayed diagnosis was mostly caused by the patients, suggesting that TB control strategy for non-residents should aim at improving the access to TB diagnosis among patients with lower income and female non-residents.

China↗

The impact of media-based health education on tuberculosis diagnosis in Cali, Colombia.

Tuberculosis (TB) is one of the most worrying infectious diseases facing less developed countries. Diagnosis and treatment of those who are transmitting Mycobacterium tuberculosis is considered a very effective control strategy. Within this strategy the priority is to achieve high cure rates before attempting to increase case finding. However, there is a dearth of research on how to increase case finding and diagnostic coverage in those settings where high cure rates are being achieved. This paper presents an evaluation of the impact on case finding of a mass media health education campaign for TB control in Cali, Colombia. The campaign aimed at increasing case finding and reducing levels of prejudice against people with TB. The impact assessment shows that the campaign produced an increase of 64% in the number of direct smears processed by the laboratories and an increase of 52% in the number of new cases of positive pulmonary TB, with respect to the previous period. Unfortunately, the effects of the campaign were short-lived. These findings have at least two important implications. First, passive case finding is likely to be an insufficient strategy to reach the operational targets of diagnostic coverage. Secondly, providing basic information about the earliest symptoms of TB and the procedures for diagnosis can increase diagnostic coverage, and thus strengthen the effect on infection risk of control programmes with high cure rates. Further research is required to identify other strategies that could, first, increase diagnostic coverage and, secondly, make the intervention effects sustainable.

Colombia↗

Diagnosis of tuberculosis.

Diagnosis of tuberculosis in children is usually based on clinical signs and symptoms, chest roentgenogram, tuberculin testing and history of contact with adult patients. The diagnostic tests for tuberculosis can be broadly divided into 2 groups: demonstration/isolation of Mycobacterium tuberculosis or one of its components [Ziehl Neelson (ZN) staining, special stains, cultures, polymerase chain reaction]; demonstration of host's response to exposure to M. tuberculosis (Mantoux test, serodiagnosis). The yield of tests used for demonstration of mycobacterium or its components is poor because of pauci-bacillary nature of disease in children. Diagnostic use of PCR is still experimental. Serodiagnosis does not have acceptable sensitivity and specificity hence, at present, does not have any role in diagnosis of tuberculosis in children. The diagnosis is suspected on history and a combination of imaging studies and Mantoux test still remains the most widely used investigation.

Child↗

Advances in bovine tuberculosis diagnosis and pathogenesis: what policy makers need to know.

The mainstay of tuberculosis diagnosis in cattle and deer has been the tuberculin skin test. Recent advances have allowed the incorporation of blood based assays to the diagnostic arsenal for both cattle and deer. Use of defined and specific antigens has allowed for improved specificity of cell mediated assays in both cattle and deer and advances in antibody tests for tuberculosis have potential for use in free-ranging and captive cervid populations. Combined use of blood-based assays with skin testing will require further understanding of the effect of skin testing on the accuracy of blood based assays. Models of experimental infection of cattle have allowed for increased understanding of natural disease pathogenesis. Differences likely exist; however, between cattle and deer in both disease distribution and primary route of inoculation in naturally infected animals.

Animals↗

[Improvement of tuberculosis diagnosis by the Mycobacteria Growth Indicator Tube (MGIT) in a developing country laboratory].

In order to improve tuberculosis diagnosis in a developing country (Senegal), we evaluated a new liquid-based medium and nonradioactive system, Mycobacteria Growth Indicator Tube (MGIT), with individual clinical specimens collected in Dakar. The main purpose was to compare the time to detection and the rate of recovery of Mycobacterium tuberculosis complex and to determine its importance with respect to Lowenstein-Jensen (LJ), a liquid-based-medium for isolation of M. tuberculosis complex. 531 specimens were processed with Mycoprep kit containing NaOH-N-acetyl L-cystein and inoculated on both LJ and MGIT and incubated at 37 degrees C for 60 days. For each medium, the recovery rate and the time to detection were recorded. Among the 531 specimens, of which 121 smears were positive, 32.5% (173/531) grew the M. tuberculosis complex. Of these, 103 were smear positive (S+) and 70 smear negative (S-). LJ recovered 54.9% (95/173) and MGIT recovered 91.9% (159/173). Disagreements were observed with 92 isolates, LJ failed to recover 78 while MGIT failed to recover 14. The overall mean time to detection was 20.1 days for LJ and 10.5 days for MGIT. MGIT has shown a better sensitivity in isolation with significant reduction in reporting culture for M. tuberculosis complex. As a simple and a nonradiometric system, it could be used in conjunction with egg-based media in developing countries laboratories.

Bacteriological Techniques↗

[Adrenal tuberculosis. Diagnosis using polymerase chain reaction].

OBJECTIVE: To present a case of a patient suffering from adrenocortical insufficiency (Addison's disease) and to demonstrate the utility of the polymerase chain reaction (PCR) in the diagnosis of adrenal cortex tuberculosis. METHODS/RESULTS: Herein we describe a patient with Addison's disease who had developed pulmonary tuberculosis a few years earlier. CT and PCR test were utilized in making the diagnosis. CONCLUSION: Although adrenocortical tuberculosis is uncommon today, it must be considered when evaluating adrenocortical insufficiency, especially if the patient has or has had tuberculosis. Although Mycobacterium tuberculosis might not be demonstrated by bacteriologic techniques, PCR can be useful in making the etiological diagnosis.

Addison Disease↗

[Specific interferon-gamma assays: a modern tool for tuberculosis diagnosis].

Compared with the tuberculin skin test, the antigen-specific interferon-gamma assays, using a combination of two antigens ESAT-6 and CFP-10, has higher specificity for the diagnosis of latent tuberculosis, better correlation with exposure to M. tuberculosis, no cross-reactivity due to BCG vaccination and less towards nontuberculous mycobacterial infection. Fewer false positive results in uninfected persons avoid the costs of unnecessary therapy and its possible side effects. In low endemic areas, interferon-y assays are useful in addition of diagnostic algorithm for individuals with suspected tuberculosis. Further studies are required to evaluate the utility of the interferon-gamma assays in specialised subgroups of patients (immunocompromised, young children, patients with extrapulmonary disease,...) and as a marker of disease activity.

Humans↗

Abdominal tuberculosis: diagnosis by laparoscopy and colonoscopy.

BACKGROUND: Histopathological confirmation in abdominal tuberculosis is difficult due to suboptimal noninvasive access to the involved area. Peritoneoscopy and colonoscopy provide semi-invasive access to the peritoneum, large intestine and ileocecal area. Information on the diagnostic yield of these two investigation in abdominal tuberculosis is scarce. OBJECTIVE: To evaluate the role of laparoscopy and colonoscopy in the diagnosis of abdominal tuberculosis. PATIENTS AND METHODS: Between January 1998 and July 2001, 34 patients were diagnosed to have abdominal tuberculosis on the basis of laparoscopy or colonoscopy. The case records of these patients were retrospectively reviewed to assess the usefulness of laparoscopy and colonoscopy in the diagnosis of abdominal tuberculosis. RESULTS: Laparoscopy was performed in 23 patients. Peritoneal tuberculosis was diagnosed in 19 of them, characterized by presence of ascites, multiple whitish tubercles, fibrous bands and adhesions, hyperaemic edematous bowel loops or dense adhesions without ascites. Multiple jejunoileal hyperemic short segments with serosal neovascularization was noticed in three patients. One patient had cecal mass with pericecal inflammatory adhesions. In three patients, laparoscopy was converted to open laparotomy due to bowel injury, extensive adhesions, and difficulty in assessing lymph nodal mass in one patient each. Peritoneal biopsy confirmed the diagnosis in 10 of the 15 (67%) patients. In one patient pericecal tissue biopsy confirmed the diagnosis. The remaining patients received therapeutic trial with anti tuberculosis treatment. All patients showed good response. Thus laparoscopy provided positive diagnosis of tuberculosis in 20/23 (87%) and positive histology in 10 of the 15 (67%) patients with peritoneal lesions. Thirteen patients underwent colonoscopy. Mucosal lesions involving terminal ileum, cecum and colon was noted in 11 patients. Colonoscopic biopsy confirmed the diagnosis in six of the 11 patients (54%). Non of these patients had any complication related to colonoscopy. CONCLUSION: Laparoscopy was safe and helped in the diagnosis of peritoneal as well as intestinal tuberculosis in 87% of patients. Colonoscopy is useful for colonic and terminal ileal lesion with a positive diagnostic yield of 54%.

Adolescent↗

Extraction of rules for tuberculosis diagnosis using an artificial neural network.

The treatment of tuberculosis (TB) is a major challenge throughout the world. The Western Cape Region of South Africa has the highest occurrence of TB in the world. Here, TB is increasing due to improperly managed treatment programmes and inadequate facilities. The development of rules to aid medical practitioners in the early and accurate diagnosis of tuberculosis should prove worthwhile. A method to extract such diagnostic rules from an artificial neural network is presented. These rules accurately represent the knowledge embedded in the "raw" TB data.

Diagnosis, Computer-Assisted↗

Cutaneous tuberculosis: diagnosis and treatment.

As we move into the 21st century, cutaneous tuberculosis has re-emerged in areas with a high incidence of HIV infection and multi-drug resistant pulmonary tuberculosis. Mycobacterium tuberculosis, Mycobacterium bovis, and the BCG vaccine cause tuberculosis involving the skin. True cutaneous tuberculosis lesions can be acquired either exogenously or endogenously, show a wide spectrum of morphology and M. tuberculosis can be diagnosed by acid-fast bacilli (AFB) stains, culture or polymerase chain reaction (PCR). These lesions include tuberculous chancre, tuberculosis verrucosa cutis, lupus vulgaris, scrofuloderma, orificial tuberculosis, miliary tuberculosis, metastatic tuberculosis abscess and most cases of papulonecrotic tuberculid. The tuberculids, like cutaneous tuberculosis, show a wide spectrum of morphology but M. tuberculosis is not identified by AFB stains, culture or PCR. These lesions include lichen scrofulosorum, nodular tuberculid, most cases of nodular granulomatous phlebitis, most cases of erythema induratum of Bazin and some cases of papulonecrotic tuberculid. Diagnosis of cutaneous tuberculosis is challenging and requires the correlation of clinical findings with diagnostic testing; in addition to traditional AFB smears and cultures, there has been increased utilization of PCR because of its rapidity, sensitivity and specificity. Since most cases of cutaneous tuberculosis are a manifestation of systemic involvement, and the bacillary load in cutaneous tuberculosis is usually less than in pulmonary tuberculosis, treatment regimens are similar to that of tuberculosis in general. In the immunocompromised, such as an HIV infected patient with disseminated miliary tuberculosis, rapid diagnosis and prompt initiation of treatment are paramount. Unfortunately, despite even the most aggressive efforts, the prognosis in these individuals is poor when multi-drug resistant mycobacterium are present. An increased awareness of the re-emergence of cutaneous tuberculosis will allow for the proper diagnosis and management of this increasingly common skin disorder.

Acquired Immunodeficiency Syndrome↗