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Background

Tanzania ranks 15th among the world's 22 countries with the largest tuberculosis burden and tuberculosis has continued to be among the major public health problems in the country. Limited data, especially in patients co infected with HIV, are available to predict the duration of time required for a smear positive pulmonary tuberculosis patient to achieve sputum conversion after starting effective treatment. In this study we assessed the sputum smear and culture conversion rates among HIV positive and HIV negative smear positive pulmonary tuberculosis patients in Dar es Salaam

Methods

The study was a prospective cohort study which lasted for nine months, from April to December 2008

Results

A total of 502 smear positive pulmonary tuberculosis patients were recruited. HIV test results were obtained for 498 patients, of which 33.7% were HIV positive.

After two weeks of treatment the conversion rate by standard sputum microscopy was higher in HIV positive(72.8%) than HIV negative(63.3%) patients by univariate analysis(P = 0.046), but not in multivariate analysis. Also after two weeks of treatment the conversion rate by fluorescence microscopy was higher in HIV positive (72.8%) than in HIV negative(63.2%) patients by univariate analysis (P = 0.043) but not in the multivariate analysis. The conversion rates by both methods during the rest of the treatment period (8, 12, and 20 weeks) were not significantly different between HIV positive and HIV negative patients.

With regards to culture, the conversion rate during the whole period of the treatment (2, 8, 12 and 20 weeks) were not significantly different between HIV positive and HIV negative patients.

Conclusion

Conversion rates of standard smear microscopy, fluorescence microscopy and culture did not differ between HIV positive and HIV negative pulmonary tuberculosis patients.

Direct smear examination with Ziehl-Neelsen (ZN) staining for the diagnosis of tuberculosis (TB) as employed in most low-income countries is cheap and easy to use, but its low sensitivity is a major drawback. The low specificity of chest X-rays, used for the diagnosis of smear-negative TB, risks high levels of overdiagnosis. Major advances in molecular techniques, which rapidly identify mycobacterial DNA in sputa, may overcome these obstacles. In this study, the AMPLICOR PCR system was used to diagnose pulmonary TB in a developing country with high prevalences of both TB and human immunodeficiency virus (HIV). The sensitivity and specificity of this technique were compared to those of the usual diagnostic techniques. Sputum specimens were collected from 1,396 TB suspects attending the Rhodes Chest Clinic, Nairobi, Kenya. The specimens were analyzed for the presence of Mycobacterium tuberculosis by PCR; culture on Löwenstein-Jensen medium was used as the “gold standard.” All culture-positive samples were genotyped to identify the mycobacterial species. The sensitivity and specificity of PCR were 93 and 84%, respectively. HIV status did not affect the sensitivity of PCR. A total of 99.7% of the true smear-positive and 82.1% of the true smear-negative TB patients were correctly identified by PCR. PCR detected M. tuberculosis in 11.7% of the culture-negative suspects, 60% of which had one or two PCR-positive sputum specimens. Of the 490 positive cultures, 486 were identified as M. tuberculosis. The high sensitivity of Amplicor PCR merits usage in a clinical setting with high TB and HIV burdens. Thus, PCR can be considered as an alternative to ZN staining in combination with chest X-ray for diagnosis of TB; however, cost-effectiveness studies and operational studies are required to support an evidence-based decision of introducing PCR for TB control in high-burden environments.

BACKGROUND: A serological test that could help to diagnose tuberculosis, especially smear negative disease, would contribute to patient management. METHODS: Levels of antibody to distinct antigens of Mycobacterium tuberculosis were assessed for their value in the diagnosis and management of pulmonary tuberculosis. Serum was taken from 52 patients who were smear positive, from 27 patients who were smear negative but with evidence of active tuberculosis (sputum culture positive in 16, response to antituberculosis chemotherapy in 11), from 11 patients with old healed tuberculosis (pre-antibiotic era), and from 39 healthy subjects vaccinated with BCG. RESULTS: In smear positive tuberculosis an enzyme linked immunosorbent assay using a single 38 kDa antigen gave a diagnostic sensitivity of 80% with a 100% specificity. In smear negative pulmonary tuberculosis, however, combination of the 19 kDa antigen, lipoarabinomannan (ML 34 epitope), and hsp 65 (TB 78 epitope) was needed to achieve a sensitivity of 64% with a specificity of 95%. Recurrent and extensive radiographic disease with a poor prognosis was associated with high anti-38 kDa and low anti-14 kDa antibody levels in patients with active disease. Patients with less pulmonary cavitation had high anti-19 kDa titres. Bacteriological relapse during treatment was indicated by a rise in anti-14 kDa (TB68 epitope) antibodies. Four patients with non-tuberculous mycobacterial infection showed no anti-38 kDa antibody. CONCLUSION: Antigen or epitope specific serology may help in the diagnosis, assessment of prognosis, and monitoring of chemotherapy in patients with pulmonary tuberculosis.

Background. Tuberculosis (TB) disease diagnosis in Vietnam relies on symptom screening, chest radiography (CXR), and acid fast bacilli (AFB) sputum smear which have a poor sensitivity in HIV patients. We evaluated the performance of clinical algorithms in screening and diagnosing AFB smear-negative TB in HIV patients. Methods. We enrolled 399 HIV-positive patients seeking care at a HIV clinic in Ho Chi Minh City (HCMC), Vietnam. Participants' demographics, medical history, common TB symptoms, CXR, and laboratory tests were collected. Results. Of 399 HIV patients, 390 had initial AFB-negative smears and 22/390 patients had positive cultures. Symptom screening missed 54% (12/22) of smear-negative pulmonary TB (PTB) cases. Multivariate analysis found CD4+ cell level and CXR were significant PTB predictors. An algorithm combining four TB symptoms and TST presented a high sensitivity (100%), but poorly specific (24%) diagnostic performance for smear-negative PTB. Conclusion. Up to 54% of PTB cases in the HIV-infected population may be missed in the routine screening and diagnostic procedures used in Vietnam. Symptom screening was a poor overall diagnostic measure in detecting smear-negative TB in HIV patients. Our study results suggest that routine sputum cultures should be implemented to achieve a more accurate diagnosis of TB in HIV patients.

The diagnostic gold standard for active tuberculosis (TB) is the detection of Mycobacterium tuberculosis (MTB) by culture or molecular methods. However, despite its limited sensitivity, sputum smear microscopy is still the mainstay of TB diagnosis in resource-limited settings. Consequently, diagnosis of smear-negative pulmonary and extrapulmonary TB remains challenging in such settings. A number of novel or alternative techniques could provide adjunctive diagnostic use in the context of difficult-to-diagnose TB. These may be especially useful in certain patient groups such as persons infected with human immunodeficiency virus (HIV) and children, who are disproportionably affected by smear-negative and extrapulmonary disease and who are also most adversely affected by delays in TB diagnosis and treatment. We review a selection of these methods that are independent of nucleic acid amplification techniques and could largely be implemented in resource-limited settings in current or adapted versions. Specifically, we discuss the diagnostic use and potential of serologic tests based on detection of antibodies to MTB antigens; interferon gamma release assays using site-specific lymphocytes; detection of lipoarabinomannan, a glycolipid of MTB, in urine; the string test, a novel technique to retrieve lower respiratory tract samples; and fine needle aspiration biopsy of lymph nodes.

Background

The 2007 WHO algorithm for diagnosis of smear-negative pulmonary tuberculosis (PTB) including Mycobacterium tuberculosis (MTB) culture was evaluated in a HIV prevalent area of Kenya.

Methods

PTB smear-negative adult suspects were included in a prospective diagnostic study (2009–2011). In addition, program data (2008–2009) were retrospectively analysed. At the first consultation, clinical examination, chest X-ray, and sputum culture (Thin-Layer-Agar and Lowenstein-Jensen) were performed. Patients not started on TB treatment were clinically re-assessed after antibiotic course. The algorithm performance was calculated using culture as reference standard.

Results

380 patients were included prospectively and 406 analyzed retrospectively. Culture was positive for MTB in 17.5% (61/348) and 21.8% (72/330) of cases. Sensitivity of the clinical-radiological algorithm was 55.0% and 31.9% in the prospective study and the program data analysis, respectively. Specificity, positive and negative predictive values were 72.9%, 29.7% and 88.6% in the prospective study and 79.8%, 30.7% and 80.8% in the program data analysis. Performing culture increased the number of confirmed TB patients started on treatment by 43.3% in the prospective study and by 44.4% in the program data analysis. Median time to treatment of confirmed TB patients was 6 days in the prospective study and 27 days in the retrospective study. Inter-reader agreement for X-ray interpretation between the study clinician and a radiologist was low (Kappa coefficient = 0.11, 95%CI: 0.09–0.12). In a multivariate logistic analysis, past TB history, number of symptoms and signs at the clinical exam were independently associated with risk of overtreatment.

Conclusion

The clinical-radiological algorithm is suboptimal to diagnose smear-negative PTB. Culture increases significantly the proportion of confirmed TB cases started on treatment. Better access to rapid MTB culture and development of new diagnostic tests is necessary.

A coagglutination technique was established for the detection of lipoarabinomannan of Mycobacterium tuberculosis in human serum samples and evaluated for its utility in the diagnosis of tuberculosis at the Instituto Nacional de Enfermedades Respiratorias in Mexico City. The test had a sensitivity of 88% in patients with sputum-smear-positive active pulmonary tuberculosis. The sensitivity in patients with active pulmonary tuberculosis negative for acid-fast bacilli in sputum was 67%. Less favorable results were obtained for patients with AIDS and tuberculosis, with a sensitivity of 57%. The specificity in control patients with lung diseases different from tuberculosis and in healthy subjects was 100%. The positive predictive value was 100%, and the negative predictive value for patients with sputum-positive active pulmonary tuberculosis was 97%. The results of this study suggest that the detection of lipoarabinomannan is an accurate test for the diagnosis of pulmonary tuberculosis.

BACKGROUND:

Smear-negative tuberculosis occurs more frequently in human immunodeficiency virus (HIV)-infected patients than in non-HIV-infected patients. Besides, there are substantial numbers of patients who cannot produce sputum, making the diagnosis of pulmonary tuberculosis (PTB) difficult.

AIMS:

To evaluate the relative yield of pre- and post-bronchoscopy sputum and bronchoalveolar lavage (BAL) in ‘sputum smear’-negative, HIV-positive patients.

SETTINGS:

A tertiary care referral hospital in Addis Ababa.

MATERIALS AND METHODS:

Acid-fast stain (AFS) using the concentration technique was done on 85 pre-bronchoscopy sputum and 120 BAL samples. Direct AFS was done on all BAL and 117 post-bronchoscopy sputum samples. Culture for Mycobacterium tuberculosis (MTB) was done for all sputa and BAL.

RESULTS:

MTB was isolated from 26 (21.7%), 23 (19.7%) and 13 (15.3%) of BAL, post- and pre-bronchoscopy sputum cultures respectively. AFS on pre-bronchoscopy sputum using concentration technique and direct AFS on BAL together detected 11 (41%) of the 27 culture-positive cases. In patients who could produce sputum, the sensitivity of pre-bronchoscopy sputum culture (13/85, 15.3%) was comparable to BAL (12/85, 14%) and post-bronchoscopy sputum (12/85, 14%). In patients who could not produce sputum, however, both BAL (12/35, 40%) and post-bronchoscopy sputum (12/32, 31.4%) detected significantly more patients than those who could produce sputum (P=0.002, P=0.028 respectively).

CONCLUSION:

In HIV-infected patients, AFS by concentration method on pre-bronchoscopy sputum and direct AFS on BAL in patients who cannot produce sputum are the preferred methods of making a rapid diagnosis. BAL culture seems to add little value in patients who can produce sputum; therefore, bronchoscopy should be deferred under such circumstances.

Three hundred twenty-four sputum specimens from 151 patients with suspected active pulmonary tuberculosis were tested for the presence of the Mycobacterium tuberculosis complex with auramine fluorochrome stain and automated PCR assay (Roche Cobas Amplicor Mycobacterium Tuberculosis Test [MTB]). The results were compared with those of the conventional Löwenstein-Jensen tube culture and the BACTEC radiometer liquid culture. A total of 76 specimens from 32 patients were culture positive for M. tuberculosis. In addition, 37 specimens from 15 patients were smear and culture positive for other Mycobacterium species but negative by the present nucleic acid amplification method and thus were not included in the comparison. Compared with culture, the sensitivities, specificities, and positive and negative predictive values for acid-fast smear were 67, 98, 93, and 91% and those for the Cobas Amplicor MTB were 83, 99, 97, and 95%, respectively. When three consecutive sputum specimens per patient could be obtained, the sensitivity of the Cobas Amplicor MTB improved to 91%, whereas the sensitivity of the acid-fast smear remained unchanged.

Background

This study was aimed to investigate the diagnostic value of fiberoptic bronchoscopy (FOB) with chest high-resolution computed tomography (HRCT) for the rapid diagnosis of active pulmonary tuberculosis (PTB) in patients suspected of PTB but found to have a negative sputum acid-fast bacilli (AFB) smear.

Methods

We evaluated the diagnostic accuracy of results from FOB and HRCT in 126 patients at Gangnam Severance Hospital (Seoul, Korea) who were suspected of having PTB.

Results

Of 126 patients who had negative sputum AFB smears but were suspected of having PTB, 54 patients were confirmed as having active PTB. Hemoptysis was negatively correlated with active PTB. Tree-in-bud appearance on HRCT was significantly associated with active PTB. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of FOB alone was 75.9%, 97.2%, 95.3%, and 84.3%, respectively, for the rapid diagnosis of active PTB. The combination of FOB and HRCT improved the sensitivity to 96.3% and the NPV to 96.2%.

Conclusions

FOB is a useful tool in the rapid diagnosis of active PTB with a high sensitivity, specificity, PPV and NPV in sputum smear-negative PTB-suspected patients. HRCT improves the sensitivity of FOB when used in combination with FOB in sputum smear-negative patients suspected of having PTB.

Background

Peripheral blood interferon-gamma release assays (IGRAs) have sub-optimal sensitivity and specificity for diagnosis of active pulmonary tuberculosis (TB). However, assessment of local immune responses has been reported to improve the accuracy of TB diagnosis.

Methods

We enrolled HIV-infected adults with cough ≥2 weeks’ duration admitted to Mulago Hospital in Kampala, Uganda and referred for bronchoscopy following two negative sputum acid-fast bacillus smears. We performed an ELISPOT-based IGRA (T-SPOT.TB®, Oxford Immunotec, Oxford, UK) using peripheral blood and bronchoalveolar lavage (BAL) fluid mononuclear cells, and determined the accuracy of IGRAs using mycobacterial culture results as a reference standard.

Results

94 HIV-infected patients with paired peripheral blood and BAL IGRA results were included. The study population was young (median age 34 years [IQR 28–40 years]) and had advanced HIV/AIDS (median CD4+ T-lymphocyte count 60 cells/µl [IQR 22–200 cells/µl]). The proportion of indeterminate IGRA results was higher in BAL fluid than in peripheral blood specimens (34% vs. 14%, difference 20%, 95% CI 7–33%, p = 0.002). BAL IGRA had moderate sensitivity (73%, 95% CI 50–89%) but poor specificity (48%, 95% CI 32–64%) for TB diagnosis. Sensitivity was similar (75%, 95% CI 57–89%) and specificity was higher (78%, 95% CI 63–88%) when IGRA was performed on peripheral blood.

Conclusions

BAL IGRA performed poorly for the diagnosis of smear-negative TB in a high HIV/TB burden setting. Further studies are needed to examine reasons for the large proportion of indeterminate results and low specificity of BAL IGRA for active TB in high HIV/TB burden settings.

Background

Rapid and accurate diagnosis of tuberculosis (TB) is crucial to facilitate early treatment of infectious cases and thus to reduce its spread. To improve the diagnosis of TB, more rapid diagnostic techniques such as antibody detection methods including enzyme-linked immunosorbent assay (ELISA)-based serological tests and immunochromatographic methods were developed. This study was designed to evaluate the validity of an immunochromatographic assay, ICT Tuberculosis test for the serologic diagnosis of TB in Antalya, Turkey.

Methods

Sera from 72 patients with active pulmonary (53 smear-positive and 19 smear-negative cases) and eight extrapulmonary (6 smear-positive and 2 smear-negative cases) TB, and 54 controls from different outpatient clinics with similar demographic characteristics as patients were tested by ICT Tuberculosis test.

Results

The sensitivity, specificity, and negative predictive value of the ICT Tuberculosis test for pulmonary TB were 33.3%, 100%, and 52.9%, respectively. Smear-positive pulmonary TB patients showed a higher positivity rate for antibodies than smear-negative patients, but the difference was not statistically significant. Of the eight patients with extrapulmonary TB, antibody was detected in four patients.

Conclusion

Our results suggest that ICT Tuberculosis test can be used to aid TB diagnosis in smear-positive patients until the culture results are available.

Background

Sputum concentration increases the sensitivity of smear microscopy for the diagnosis of tuberculosis (TB), but few studies have investigated this method in human immunodeficiency virus (HIV)-infected individuals.

Methods

We performed a prospective, blinded evaluation of direct and concentrated Ziehl-Neelsen smear microscopy on a single early-morning sputum sample in HIV-infected patients with > 2 weeks of cough hospitalized in Kampala, Uganda. Direct and concentrated smear results were compared with results of Lowenstein-Jensen culture.

Results

Of 279 participants, 170 (61%) had culture-confirmed TB. The sensitivity of direct and concentrated smear microscopy was not significantly different (51% vs. 52%, difference 1%, 95% confidence interval (CI): [-7%, 10%], p = 0.88). However, when results of both direct and concentrated smears were considered together, sensitivity was significantly increased compared with either method alone (64%, 95% CI: [56%, 72%], p < 0.01 for both comparisons) and was similar to that of direct smear results from consecutive (spot and early-morning) specimens (64% vs. 63%, difference 1%, 95% CI: [-6%, 8%], p = 0.85). Among 109 patients with negative cultures, one had a positive direct smear and 12 had positive concentrated smears (specificity 99% vs. 89%, difference 10%, 95% CI: [2%, 18%], p = 0.003). Of these 13 patients, 5 (38%) had improved on TB therapy after two months.

Conclusion

Sputum concentration did not increase the sensitivity of light microscopy for TB diagnosis in this HIV-infected population. Given the resource requirements for sputum concentration, additional studies using maximal blinding, high-quality direct microscopy, and a rigorous gold standard should be conducted before universally recommending this technique.

A rapid membrane-based serologic assay using the 38-kDa antigen from Mycobacterium tuberculosis for the diagnosis of tuberculosis (TB) was evaluated with 201 patients with pulmonary TB, 67 patients with extrapulmonary TB, 79 Mycobacterium bovis BCG-vaccinated healthy controls, and 77 non-TB respiratory patients. The overall sensitivities, specificities, and positive and negative predictive values were, respectively, 92, 92, 84, and 96% for sputum-positive TB patients; 70, 92, 87, and 79% for sputum-negative TB patients; and 76, 92, 80, and 90% for extrapulmonary-TB patients. Only 2% (1 of 44) of the healthy control BCG-vaccinated subjects gave weak positive signals in the assay, indicating that this rapid serological assay is a valuable aid in clinical diagnosis for both pulmonary and extrapulmonary TB.

A repetitive sequence of Mycobacterium tuberculosis DNA was amplified by polymerase chain reaction (PCR), from sputum samples, for the diagnosis of pulmonary tuberculosis. The method of heating the sample in a boiling water bath to break down the bacterial cell wall and to release the DNA was compared with that of enzymatic lysis of bacteria and then phenol-chloroform extraction of DNA. Heating the sample was the better method with a sensitivity of approximately 10 microorganisms. A total of 78 sputum specimens prepared by heating were examined by PCR, and the results were compared with the results of acid-fast stained smears, cultures, and clinical data. M. tuberculosis was detected by PCR in all smear- and culture-positive and smear-negative, culture-positive cases. Additionally, PCR was capable of detecting four of nine cases which were smear and culture negative but clinically suspected of tuberculosis. DNA amplification by PCR is a sensitive and specific method for the diagnosis of tuberculosis, and with this simplified DNA isolation procedure it can be used in routine clinical practice.

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Background

Effective tuberculosis (TB) control in HIV-prevalent settings is hindered by absence of accurate, rapid TB diagnostic tests. We evaluated the accuracy of a urine lipoarabinomannan (LAM) test for TB diagnosis in South Africa.

Methods

Hospitalized adults with signs and/or symptoms of active TB were enrolled. Sputum smear microscopy and mycobacterial culture, mycobacterial blood culture, and HIV testing were performed. A spot urine specimen was tested for LAM.

Results

499 participants were enrolled; 422 (84.6%) were HIV-infected. In microbiologically-confirmed TB patients, the LAM test was positive in 114/193 (sensitivity 59%, [95% CI 52, 66]), including 112/167 (67% [59, 74]) who were HIV-infected. Among individuals classified as “not TB”, the LAM test was negative in 117/122 (specificity 96% [91, 99]), including 83/88 (94% [87, 98]) who were HIV-infected. In confirmed TB patients, the LAM test was more sensitive than sputum smear microscopy (42%, 82/193, p<0.001) and detected 56% (62/111) of those who were sputum smear-negative. HIV-infection (AOR 13.4), mycobacteremia (AOR 3.21), and positive sputum smear (AOR 2.42) were risk factors for a positive LAM test.

Conclusions

The urine LAM test detected a subset of HIV-infected patients with severe TB in whom sputum smear microscopy had suboptimal sensitivity. The combination of urine LAM testing and sputum smear microscopy is attractive for use in settings with high HIV burden.

We evaluated the immunoglobulin G (IgG) antibody response to the 45/47-kDa secreted protein of Mycobacterium tuberculosis by immunoblot assay, to assess its potential value for serological diagnosis. Control subjects consisted of healthy volunteers with negative or positive tuberculin skin tests. Most (>98%) scored negative in an immunoblot test when the sera were analyzed at a 1:400 dilution. Approximately 40% of sera (diluted 1 in 400) from tuberculous patients (positive smears) recognized the antigen complex. The sensitivity of the test for patients suffering from extrapulmonary tuberculosis was similar to that for patients suffering from pulmonary tuberculosis but who had negative smears. The frequency of positive reactions among the patients suffering from other pulmonary diseases was similar to that among the control subjects. In tuberculous patients infected with human immunodeficiency virus, the sensitivity of the immunoblot test was significantly lower. Thus, this test based on an antigen complex used in an immunoblot assay to detect the presence of IgG antibody has a specificity of 98% and a sensitivity of 40%. The simultaneous use of different purified antigens, selected at the same high specificity level, may improve the sensitivity of such an assay.

We conducted a meta-analysis to assess the performance of PCR for the diagnosis of smear-negative pulmonary tuberculosis (SPT) and to identify factors that account for differences in the diagnostic accuracy of different studies. Studies published before February 2002 were included if sensitivity and specificity of PCR in smear-negative respiratory or gastric-aspirate specimens could be calculated. Analysis was conducted by using summary receiver operating characteristics models. Sensitivity and specificity ranged from 9 to 100% and from 25 to 100%, respectively. Fewer than 40% of the 50 studies reported results by number of patients, reported clinical characteristics of patients, or used as a reference standard combined culture and clinical criteria. Studies that included bronchial specimens showed higher accuracy than studies that evaluated only sputum specimens or included gastric aspirates. Studies that did not report that tests were applied blindly showed higher accuracy than those reporting blind testing. Increased sensitivity due to the use of DNA purification methods was associated with decreased specificity. Studies published after 1995, using Amplicor or dUTP-UNG, were associated with an increase in specificity at the expense of lower sensitivity. We concluded that PCR is not consistently accurate enough to be routinely recommended for the diagnosis of SPT. However, PCR of bronchial specimens could be useful in highly suspicious SPT cases. Studies not reporting blind testing are likely to overestimate accuracy of PCR. Future evaluation of PCR accuracy should be conducted by patient and type of respiratory specimen, blindly, by using a reference standard that combines culture and clinical criteria and addresses the issue of how patient characteristics affect PCR accuracy.

Background

Clinical suspects of pulmonary tuberculosis in which the sputum smears are negative for acid fast bacilli represent a diagnostic challenge in resource constrained settings. Our objective was to validate an existing clinical-radiographic score that assessed the probability of smear-negative pulmonary tuberculosis (SNPT) in high incidence settings in Peru.

Methodology/Principal Findings

We included in two referral hospitals in Lima patients with clinical suspicion of pulmonary tuberculosis and two or more negative sputum smears. Using a published but not externally validated score, patients were classified as having low, intermediate or high probability of pulmonary tuberculosis. The reference standard for the diagnosis of tuberculosis was a positive sputum culture in at least one of 2 liquid (MGIT or Middlebrook 7H9) and 1 solid (Ogawa) media. Prevalence of tuberculosis was calculated in each of the three probability groups.

684 patients were included. 184 (27.8%) had a diagnosis of pulmonary tuberculosis. The score did not perform well in patients with a previous history of pulmonary tuberculosis. In patients without, the prevalence of tuberculosis was 5.1%, 31.7% and 72% in the low, intermediate and high probability group respectively. The area under de ROC curve was 0.76 (95% CI 0.72–0.80) and scores ≥6 had a positive LR of 10.9.

Conclusions/Significance

In smear negative suspects without previous history of tuberculosis, the clinical-radiographic score can be used as a tool to assess the probability of pulmonary tuberculosis and to guide the decision to initiate or defer treatment or to requesting additional tests.

Background

In patients with HIV and tuberculosis (TB) in resource-constrained settings, smear-negative disease has been associated with higher mortality than smear-positive disease. Higher reported mortality may be due to misdiagnosis, diagnostic delays, or because smear-negative disease indicates more advanced immune suppression.

Methods

We analyzed culture-confirmed, pulmonary TB among patients with TB and HIV in the United States from 1993–2008 to calculate prevalence ratios (PRs) for smear-negative disease by demographic and clinical characteristics. Allowing two years for treatment outcome to be reported, we determined hazard ratios (HRs) for survival by smear status, adjusted for significant covariates on patients before 2006.

Results

Among 16,710 cases with sputum smear results, 6,739 (39%) were sputum smear-negative and 9,971 (58%) were sputum smear-positive. The prevalence of smear-negative disease was lower in male patients (PR: 0.89, 95% confidence interval [CI]: 0.86–0.93) and in those who were homeless (PR: 0.92, CI: 0.87–0.97) or used alcohol excessively (PR: 0.91, CI: 0.87–0.95), and higher in persons diagnosed while incarcerated (PR: 1.20, CI: 1.13–1.27). Patients with smear-negative disease had better survival compared to patients with smear-positive disease, both before (HR: 0.82, CI: 0.75–0.90) and after (HR: 0.81, CI: 0.71–0.92) the introduction of combination anti-retroviral therapy.

Conclusions

In the United States, smear-negative pulmonary TB in patients with HIV was not associated with higher mortality, in contrast to what has been documented in high TB burden settings. Smear-negative TB can be routinely and definitively diagnosed in the United States, whereas high-burden countries often rely solely on AFB-smear microscopy. This difference could contribute to diagnostic and treatment delays in high-burden countries, possibly resulting in higher mortality.

Context:

About 30 to 50 % of pulmonary tuberculosis patients have sputum report negative for acid fast bacilli or present with no expectoration. A lot of research is going on to find methods to establish early and accurate diagnosis of pulmonary tuberculosis (PTB) as institutions of early treatment can have significant effects on morbidity and mortality of patients and also the development of MDR–TB. Samples other than sputum play an important role in the diagnosis of disease in such patients.

Aims:

To assess the significance of bronchoalveolar lavage samples and fiberoptic bronchoscopy (FOB) in the early diagnosis of occult sputum smear negative pulmonary tuberculosis.

Settings and Design:

Study was conducted in a tertiary care hospital. FOB was performed in patients with three consecutive sputum smear negative acid fast bacilli to obtain bronchoalveolar lavage (BAL) samples. Written informed consent was obtained from these patients.

Materials and Methods:

BAL samples were subjected to Z-N staining and culture on L-J slopes for acid fast bacilli. Sputum samples from the same patients were also cultured.

Results:

BAL samples were positive in 82.2% of sputum smear negative samples. Culture positivity of BAL samples was 90.9% as compared to sputum culture positivity which was 26.4%. Overall diagnosis could be established in 86.6% of patients with the help of fiber optic bronchoscopy.

Conclusions:

BAL samples are very useful in early sputum smear negative pulmonary tuberculosis and FOB can play an important role in diagnosis of lower respiratory tract infections with minimal complications in hands of an expert.

Background:

Diagnosis of sputum/smear-negative pulmonary tuberculosis patients can be both challenging and time consuming with many patients being put on empirical anti-tubercular treatment. Fibreoptic bronchoscopy may provide a confirmative and early diagnosis in such patients.

Aims:

To assess the role of fibreoptic bronchoscopy in the diagnosis of sputum /smear-negative pulmonary tuberculosis.

Materials and Methods:

The study was conducted on 75 suspected sputum / smear-negative pulmonary tuberculosis cases attending Pulmonary Medicine Department of Mamata Medical College and Hospital, Khammam, AP. Fibreoptic bronchoscopy was performed; culture of sputum and bronchial washings for Mycobacterium tuberculosis was done by BACTEC method.

Results:

A final diagnosis of sputum /smear-negative pulmonary tuberculosis was made in 60 patients. Bronchial washings smear for acid-fast bacilli (AFB) was positive in 21 patients while culture of bronchial washings was positive in 39 patients. In 29 patients, smear or culture of bronchial washing alone contributed to the final diagnosis. Total yield of bronchoscopy in diagnosis of sputum smear negative pulmonary tuberculosis was 83.33% (50/60); bronchoscopy was the only diagnostic method in 66% cases (40/60) with bronchial washings being the only diagnostic method in 48.33%. Bronchial washings smear for AFB and histopathological evidence of caseating granuloma made immediate diagnosis possible in 48.33% (29/60) patients.

Conclusion:

Our study suggests that fibreoptic bronchoscopy can provide excellent material for diagnosis of suspected cases of Pulmonary Tuberculosis in whom smears of expectorated sputum do not reveal mycobacteria.

The GeneXpert MTB/RIF assay was evaluated with microscopically negative and positive pulmonary and extrapulmonary specimens from patients with substantial clinical indications for tuberculosis. For the pulmonary samples, the sensitivity, specificity, and positive and negative predictive values were 90.6%, 94.3%, 93.5%, and 91.7%, and for the extrapulmonary samples, they were 100%, 91.6%, 50%, and 100%, respectively. For microscopically negative specimens, the respective values were 86.3%, 93%, 79%, and 95.6%. The assay correctly detected rifampin resistance in all but one specimen, which harbored a mixed population. The GeneXpert assay was highly effective for tuberculosis diagnosis and identification of rifampin-resistant strains in smear-negative samples.

A serological survey was performed in groups of patients with active sputum smear-positive or smear-negative pulmonary tuberculosis, healthy household contacts, and controls. Sera were tested for titers of antibodies which bound to each of five purified mycobacterial antigens by enzyme immunoassay and for competition of binding to single epitopes, using six radiolabeled monoclonal antibodies directed toward corresponding molecules. The evaluation of diagnostic specificity was based on a positive score represented by titers above the cutoff point of 2 standard deviations above the mean titer of a control group. For smear-positive samples, the best sensitivity (83%) was achieved by exclusive use of the 38-kilodalton (kDa) antigen or its corresponding monoclonal antibodies. For smear-negative samples, levels of antibodies binding to the 19-kDa antigen showed a lower sensitivity of 62% compared with the control group or 38% compared with the contact group. Titers of antibody binding to the 14-kDa antigen were raised in Mycobacterium bovis BCG-vaccinated contacts, indicating that the greatest potential of this antigen may be in the detection of infection in a population for which tuberculin testing is unreliable. The results demonstrated the differing antibody responses to each of the tested antigens and distinct associations with the stage of infection or disease.

Objectives: To study the positivity of sputum acid fast bacilli (AFB) smears in patients with pulmonary tuberculosis using 24 hour sputum collection. To detect HIV seropositivity in patients suffering from tuberculosis, and to analyse the pattern of tuberculosis disease in this subgroup. To determine the outcome of patients treated with directly observed therapy.

Setting: The tuberculosis referral unit of a tertiary care hospital.

Design: A total of 893 consecutive patients with tuberculosis, diagnosed between 1 November 2000 and 30 September 2002, were included in the study. An HIV test was performed in all patients, with adequate counselling and informed consent. Treatment was prescribed as per World Health Organisation treatment categories.

Results: Out of 893 patients with tuberculosis, 695 had pulmonary tuberculosis and 198 had extrapulmonary tuberculosis. Out of the 695 pulmonary tuberculosis patients, 673 (96.8%) were sputum smear AFB positive. Overall, 71 patients (8.0%) were HIV positive. The pattern of tuberculosis was the same in HIV seropositive and seronegative patients. Treatment outcome could be analysed in 112 out of 150 patients: 78 patients (70%) were declared cured or completed treatment.

Conclusions: Sputum smear AFB could be a very sensitive test when a large quantity of sputum is used. The presence of HIV coinfection does not alter the clinical presentation. Only 70% of patients treated were cured/completed treatment, in spite of a strict directly observed therapy.