The rapid diagnosis of smear-negative pulmonary tuberculosis: a cost-effectiveness analysis

OBJECTIVE: The prompt diagnosis of smear-negative pulmonary tuberculosis (PTB) is a clinical challenge. It may be achieved by a number of tests which have varying accuracies, costs and degrees of invasiveness. The objective of this study was to compare the cost-effectiveness of clinical judgement (empirical), the Roche Cobas amplicor assay for Mycobacterium tuberculosis (amplicor), acid-fast staining of bronchoalveolar lavage specimens (BAL), nucleic acid amplification tests of bronchoalveloar lavage specimens for M. tuberculosis (BAL + NAA), computed tomography (CT) and amplicor assay followed by BAL. METHODOLOGY: The range of predictive values of the various strategies were derived from published data and a new study of 441 consecutive adult patients with suspected smear-negative PTB prospectively stratified into three pretest risk groups: low, intermediate and high. The cost-effectiveness was evaluated with a decision tree model (DATA software). RESULTS: The incidence of PTB was 5.7% (4% culture positive) for the whole group, 95% in the high-risk group, 0.9% in the low-risk group and 3.4% in the intermediate-risk group. The sensitivity of the empirical approach was 49% and of the amplicor assay was 44%. Patient outcomes were expressed as life expectancy for the base case of a 58-year-old man with a pretest probability of 5.7%. At this low pretest risk the differences in life expectancies between tests was < 0.1 years and the empirical approach incurred the lowest cost. Sensitivity analysis at increasing pretest risks showed better life expectancies (approximately 1 years) for CT scan and test combinations than empirical and amplicor for additional costs of US$243-US$309. Bronchoalveolar lavage had the worst overall cost-effectiveness. CONCLUSIONS: We conclude that the pretest risk of active PTB was a key determinant of test utility; that the AMPLICOR assay was comparable to clinical judgement; that BAL was the least useful test; and that with increasing risks, CT scan and test combinations performed better. Further studies are needed to better define patients with intermediate risk for PTB and to directly compare the cost-effectiveness of more sensitive nucleic acid amplification tests such as the enhanced Gen Probe, CT scan and test combinations/sequences in these patients.     

What is the optimal approach for using a direct amplification test in the routine diagnosis of pulmonary tuberculosis? A preliminary assessment

OBJECTIVE: The aim of this study was to determine the most appropriate strategy for the rapid diagnosis of pulmonary tuberculosis (PTB) using a nucleic acid amplification (NAA) test. METHODOLOGY: This was a prospective study of 128 adult patients in whom respiratory secretions were tested for Mycobacterium tuberculosis by the AMPLICOR assay. The basis for starting PTB treatment was noted for each patient. The optimal approach was determined by using Bayes' theorem to compare different combinations of pretest probability, smear results with the AMPLICOR test. RESULTS: The incidence of PTB was 15.6%. In only one patient was treatment for PTB commenced because of a positive AMPLICOR result. The rest were managed according to the conventional approach which relied upon clinical judgment and direct smear. The optimal approach was to treat patients with high or intermediate pretest risk for PTB who returned positive AMPLICOR tests. The overall accuracies of the conventional approach, AMPLICOR test and optimal approach were 89.8, 95.3 and 96.1%, respectively. CONCLUSION: This small study suggests that NAA testing be limited to patients with high or intermediate pretest risk of PTB. In this group, positive results demand treatment while the management of those with negative results still relies on clinical judgment.     

Role of clinical judgment in the application of a nucleic acid amplification test for the rapid diagnosis of pulmonary tuberculosis

BACKGROUND: Several nucleic acid amplification (NAA) tests for Mycobacterium tuberculosis (MTB) have been licensed for the rapid diagnosis of active pulmonary tuberculosis (PTB) in respiratory secretions. There is uncertainty however regarding the practical application of these tests in clinical decision making. OBJECTIVE: To evaluate the utility of the COBAS AMPLICOR assay (Roche Diagnostics; Singapore) for MTB as applied by specialists for the rapid diagnosis of PTB in the routine clinical setting. DESIGN: A prospective study of consecutive patients suspected of PTB and tested with the AMPLICOR assay under the care of respiratory physicians. The final diagnosis was based on all relevant clinical information after at least 3 months of follow-up. Accuracy of the NAA test was compared with that of the initial expectant treatment. Expectant treatment was based on an integrated approach that incorporated clinical evaluation with results of direct smear and NAA tests. RESULTS: The incidence of PTB in 168 patients was 32%. The basis for expectant treatment of PTB was positive smear result in 47%, clinical suspicion in 26%, and positive AMPLICOR result in 23%. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the AMPLICOR test were 77%, 100%, 99%, 90%, and 93%, respectively. In comparison, they were 96%, 97%, 94%, 98%, and 97%, respectively, for the integrated clinical approach. CONCLUSIONS: In the rapid diagnosis of PTB, the clinical judgment of specialists augmented the utility of the NAA test: (1) specialists selected patients with high-to-moderate pretest probabilities, (2) they commenced treatment promptly on a positive NAA test result, and (3) they were willing to start treatment in some patients on the basis of high clinical suspicion despite negative smear and negative NAA test results.     

The diagnosis of smear-negative pulmonary tuberculosis: the practice of sputum smear examination in Malawi.

SETTING: Forty hospitals in Malawi (3 central, 22 district and 15 mission) performing smear microscopy and registering tuberculosis patients. OBJECTIVE: To determine, in patients aged 15 years or above, 1) the proportion with smear-negative pulmonary tuberculosis (PTB) who had sputum smears examined, 2) the number of sputum smears examined per patient, and 3) the proportion of patients registered with smear-positive and smear-negative PTB. DESIGN: Data collection during three 6-month periods, from January 1997 to June 1998, using tuberculosis registers, laboratory sputum registers and quarterly reports. RESULTS: Of 6301 smear-negative PTB patients, 84% had sputum smears examined, the rate increasing from 76% in January-June 1997, to 85% in July-December 1997, to 89% in January-June 1998. Of patients who submitted sputum (where the number of smears was recorded), 99% had two or more smears examined and 93% had three smears examined. In district and mission hospitals performance improved over time, while in central hospitals results were more variable. During the same 18-month period 21 422 patients aged 15 years or more were registered with PTB: 59% with smear-positive PTB and 41% with smear-negative PTB; this pattern was similar in each 6-month period. CONCLUSION: The study suggests that it is reasonable to aim for a target of 90% or more of smear-negative PTB patients having sputum smears examined.     

Fiberoptic bronchoscopy for the rapid diagnosis of smear-negative pulmonary tuberculosis

ABSTRACT: 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.     

Mortality rates and recurrent rates of tuberculosis in patients with smear-negative pulmonary tuberculosis and tuberculous pleural effusion who have completed treatment.

SETTING: Queen Elizabeth Central Hospital, Blantyre, and Zomba Central Hospital, Zomba, Malawi. OBJECTIVE: To follow-up human immunodeficiency virus (HIV) seropositive and HIV-seronegative patients with smear-negative pulmonary tuberculosis (PTB) and pleural TB who had completed treatment with two different regimens in Blantyre and Zomba, and to assess rates of mortality and recurrent TB. DESIGN: Patients with smear-negative and pleural TB who had completed 8 months ambulatory treatment in Blantyre or 12 months standard treatment in Zomba and who were smear and culture negative for acid-fast bacilli at the completion of treatment were actively followed every 4 months for a total of 20 months. RESULTS: Of 248 patients, 150 with smear-negative PTB and 98 with pleural TB, who completed treatment and were enrolled, 205 (83%) were HIV-positive. At 20 months, 145 (58%) patients were alive, 85 (34%) had died and 18 (7%) had transferred out of the district. The mortality rate was 25.7 per 100 person-years, with increased rates strongly associated with HIV infection and age >45 years. Forty-nine patients developed recurrent TB. The recurrence rate of TB was 16.1 per 100 person-years, with increased rates strongly associated with HIV infection, having smear-negative PTB and having received 'standard treatment'. CONCLUSION: High rates of mortality and recurrent TB were found in patients with smear-negative PTB and pleural effusion during 20 months of follow-up. TB programmes in sub-Saharan Africa must consider appropriate interventions, such as co-trimoxazole and secondary isoniazid prophylaxis, to reduce these adverse outcomes.     

Meta分析评价AMPLICOR检测系统对结核病的诊断价值

目的用Meta分析综合评价AMPLICOR检测系统对结核病的诊断价值。方法搜索Medline数据库,检索用AMPLICROR检测系统诊断结核病的文献,摘录相关数据。数据分析用Sigmaplot软件绘制SROC曲线,用Cochrane工作组的Revman4．2软件进行Meta分析,用非参数检验比较不同金标准和不同标本类型对结果的影响。结果共获得到文献42篇,AMPLICOR检测系统诊断结核病敏感性81．2％,特异性96．0％,22篇文献分别分析了AMPLICOR检测系统对涂片阳性和阴性结果的差异,对涂片阳性病例敏感性97．0％,特异性76．6％,涂片阴性病例敏感性62．2％,特异性99．3％,采用不同金标准和不同标本类型DOR(Diagnostic Odd Ratio)有显著差异。结论AMPLICROR检测系统不仅对菌阳结核病,对菌阴结核病也具有一定诊断价值。影响试验结果的因素包括金标准的类型、菌阳标本所占比例、呼吸道标本所占比例等。     

支气管肺泡灌洗液行Xpert MTB/RIF检测对涂阴肺结核的诊断价值

目的评价支气管肺泡灌洗液行Xpert MTB/RIF检测对涂阴肺结核的诊断价值。方法选取从2014年11月至2015年12月徐州市传染病医院收治的3次痰涂片阴性的可疑肺结核患者110例,对所有患者行支气管镜检查进行刷检及收集BALF,进行涂片镜检找抗酸杆菌、结核分枝杆菌培养及Xpert MTB/RIF检测,同时进行诊断。分别以BALF的罗氏培养结果及临床诊断标准作为肺结核诊断的阳性标准,计算Xpert MTB/RIF诊断涂阴肺结核的敏感度、特异度、阳性预测值及阴性预测值。结果以BALF培养阳性结果作为判断肺结核的阳性标准,BALF行Xpert MTB/RIF检测对诊断涂阴肺结核的敏感度、特异度、阳性预测值、阴性预测值分别为100%、97.4%、97.8%、100%。以临床诊断标准为诊断肺结核的阳性标准,BALF行Xpert MTB/RIF检测对诊断涂阴肺结核的敏感度、特异度、阳性预测值、阴性预测值分别为81.9%、97.4%、98.3%、74.0%。以DST结果为金标准,Xpert MTB/RIF检测利福平耐药的敏感度、特异度分别为75.0%、96.0%。结论BALF行Xpert MTB/RIF检测在涂阴肺结核中的敏感度、特异度均较高,且检测快速并能判断是否利福平耐药,对涂阴肺结核的快速诊断及治疗具有较大的应用价值。     

Useful clues to the presence of smear-negative pulmonary tuberculosis in a West African city.

OBJECTIVE: Tuberculosis suspects with negative sputum smears for acid-fast bacilli (AFB) may have either pulmonary tuberculosis (PTB) or some other pulmonary disease (non-PTB). The aim of this study was to improve the differentiation between PTB and non-PTB. DESIGN: We enrolled 396 tuberculosis suspects 15 years of age or older who had cough of 21 days or longer and three negative AFB smears. Non-PTB was diagnosed by clinical and radiographic responses to amoxicillin; smear-negative PTB was diagnosed by positive culture for Mycobacterium tuberculosis or response to antituberculosis chemotherapy. RESULTS: Multivariate analysis, without X-ray variables, of 79 patients with a final diagnosis of non-PTB and 110 patients with smear-negative PTB indicated that age less than 37 years, family contact with TB, never having been married, loss of weight, lack of expectoration, human immunodeficiency virus (HIV) seropositivity, and tuberculin reactivity were significantly associated with PTB. When the initial X-ray findings were included, age younger than 37 years, lack of expectoration, HIV seropositivity, and tuberculin reactivity remained in the model, and cavitation and patchy densities were significantly associated. CONCLUSION: The response to 10 days of amoxicillin and certain demographic, clinical and radiographic characteristics are useful in separating non-PTB from PTB in tuberculosis suspects with negative AFB smears.     

High early death rate in tuberculosis patients in Malawi.

SETTING: Thirty-eight district and mission hospitals in Malawi. OBJECTIVES: In patients registered with all types of tuberculosis (TB) in 1997 to determine 1) treatment outcomes, and 2) when in the course of anti-tuberculosis treatment TB deaths occurred. DESIGN: A retrospective study using information from TB registers, health centre registers, TB treatment cards and TB ward admission books. RESULTS: A total of 16,004 patients were registered with all types of TB, 6471 with smear-positive pulmonary tuberculosis (PTB), 5305 with smear-negative PTB and 4228 with extra-pulmonary tuberculosis (EPTB). Of patients with all types of TB, 3720 (23%) died: death rates were 22% in smear-positive PTB, 26% in smear-negative PTB and 22% in EPTB. Month of death was known in 3371 patients (91% of those who died) and day of death in 3326 patients (89% of those who died). In patients who died, 19% of deaths occurred by day 7 and 41% by the end of the first month of treatment. A higher proportion of early deaths occurred in patients with smear-negative PTB and EPTB and in relation to increasing age. CONCLUSIONS: There was a high overall death rate in TB patients registered in 1997, with 40% of deaths occurring in the first month of treatment. Strategies to combat this problem are needed.     

Clinical diagnosis of smear-negative pulmonary tuberculosis: an audit of diagnostic practice in hospitals in Malawi.

SETTING: Thirty-seven hospitals in Malawi. OBJECTIVE: To audit the hospital practice of clinically diagnosing adults with smear-negative pulmonary tuberculosis (PTB). DESIGN: A cross-sectional survey of adults aged 15 years or above who were registered and receiving inpatient treatment for smear-negative PTB. An assessment of each patient was carried out to determine 1) the number of recommended diagnostic guidelines (cough >3 weeks, no response to antibiotics, negative sputum smears and a chest radiograph compatible with PTB) used by hospital staff in making the diagnosis of PTB, and 2) whether the clinical diagnosis of smear-negative PTB was correct according to criteria set by the study. RESULTS: There were 259 patients, 127 men and 132 women, with a mean age of 37 years; 93% had a cough >3 weeks, 95% had received one or more courses of antibiotics, 92% had submitted sputum samples for smear examination and 97% had chest radiographs performed. In 148 (57%) patients, all four diagnostic guidelines were used, and in 238 (92%) patients three or more were used. The diagnosis of smear-negative PTB was considered correct by study criteria in 203 (78%) patients. In the remainder, 22 (8%) were considered to have extrapulmonary TB and 34 (14%) another diagnosis. CONCLUSION: Hospital practices in the diagnosis of smear-negative PTB are reasonable, although there is room for improvement with in-service training and regular audits of practice.     

Undiagnosed tuberculosis in a community with high HIV prevalence: implications for tuberculosis control

BACKGROUND: Although failure of tuberculosis (TB) control in sub-Saharan Africa is attributed to the HIV epidemic, it is unclear why the directly observed therapy short-course (DOTS) strategy is insufficient in this setting. We conducted a cross-sectional survey of pulmonary TB (PTB) and HIV infection in a community of 13,000 with high HIV prevalence and high TB notification rate and a well-functioning DOTS TB control program. METHODS: Active case finding for PTB was performed in 762 adults using sputum microscopy and Mycobacterium tuberculosis culture, testing for HIV, and a symptom and risk factor questionnaire. Survey findings were correlated with notification data extracted from the TB treatment register. RESULTS: Of those surveyed, 174 (23%) tested HIV positive, 11 (7 HIV positive) were receiving TB therapy, 6 (5 HIV positive) had previously undiagnosed smear-positive PTB, and 6 (4 HIV positive) had smear-negative/culture-positive PTB. Symptoms were not a useful screen for PTB. Among HIV-positive and -negative individuals, prevalence of notified smear-positive PTB was 1,563/100,000 and 352/100,000, undiagnosed smear-positive PTB prevalence was 2,837/100,000 and 175/100,000, and case-finding proportions were 37 and 67%, respectively. Estimated duration of infectiousness was similar for HIV-positive and HIV-negative individuals. However, 87% of total person-years of undiagnosed smear-positive TB in the community were among HIV-infected individuals. CONCLUSIONS: PTB was identified in 9% of HIV-infected individuals, with 5% being previously undiagnosed. Lack of symptoms suggestive of PTB may contribute to low case-finding rates. DOTS strategy based on passive case finding should be supplemented by active case finding targeting HIV-infected individuals.     

痰与支气管肺泡灌洗液结核分枝杆菌FQ-PCR检测对涂阴肺结核诊断价值的比较

目的 探讨呼吸道痰标本和支气管肺泡灌洗液(BALF)Mtb-DNA检测对涂阴肺结核的诊断价值。方法 选择福州肺科医院2009年7月至2009年12月胸部影像学疑为肺结核但至少3份痰涂片镜检Mtb阴性,或胸部影像学无法排除肺结核需进一步检查的患者共51例,所有入选患者初诊根据临床症状、体征、胸部影像学结果分为疑似结核组（24例）和待排结核组（27例）。均行抗结核抗体、红细胞沉降率检测及PPD试验,应用实时荧光定量聚合酶链反应（FQ-PCR）定性及定量检测两组患者痰和BALF中的Mtb-DNA。结果 疑似结核组和待排结核组各有22例和2例确诊肺结核,确诊的24例中痰FQ-PCR敏感度为45.8%（11/24）,特异度为96.3%（26/27）,Youden指数42.1%;BALF FQ-PCR的敏感度为75.0%（18/24）,特异度96.3%（26/27）,Youden指数71.3%。结论 FQ-PCR检测BALF Mtb较痰更为敏感,对影像学疑诊但痰涂片阴性的结核患者有很高的实用价值,尤其适用于无痰的患者。     

A preliminary report on pulmonary tuberculosis in patient travelers to a rural hospital of South India

BACKGROUND: Occurrence of pulmonary tuberculosis (PTB) among patient travelers in private rural hospitals are often unknown. OBJECTIVES: The aims of the study were to know the occurrence of PTB among patient travelers visiting PES hospital and to create an information and awareness in the establishment of revised national tuberculosis control program (RNTCP) in PES hospital. PATIENT AND METHODS: Adult patients (18-49yr) with TB-like chest symptoms traveling from different regions to Kuppam were included. Children, pregnant women and critically ill were excluded. Between January-December 2004, 372 such patients visited PES hospital. Two consecutive sputum samples were screened for AFB detection by Ziehl-Neelsen. Presence of AFB in both the smears was considered smear positive TB. Negative smears with X-ray abnormality was considered smear-negative TB. Anti-tubercular drugs were prescribed for TB patients. RESULTS: Of 372 patients visited, 29% were diagnosed as TB. Smear-positive and smear-negative TB were 16.6% and 12.3%, respectively. TB among females (31/113) and males (77/259) were 27.4% and 29.7%, respectively. The peak input of patients was in the months of May (53), March (48) and December (35). CONCLUSION: There is an urgent need for establishment of RNTCP in PES hospital.     

Pneumocystis jiroveci pneumonia and other pulmonary infections in TB smear-negative HIV-positive patients with atypical chest X-ray in Ethiopia

Pneumocystis pneumonia (PCP) has been considered a rare disease in sub-Saharan Africa. However, a rising prevalence has been noted recently. The objective of this study was to determine the relative prevalence of PCP and other pulmonary opportunistic diseases in patients infected with HIV in Ethiopia. 131 consecutive patients with respiratory symptoms and atypical chest X-ray, who were sputum smear-negative for AFB and seroreactive for HIV, underwent clinical evaluation and investigation for Pneumocystis jiroveci and Mycobacterium tuberculosis from sputum and bronchoalveolar lavage (BAL), and fungal and bacterial pathogens from BAL alone. Bacterial infections, Pneumocystis pneumonia (PCP) and pulmonary tuberculosis (PTB) occurred in 44 (33.6%), 39 (29.7%) and 31 (23.7%) patients, respectively. Pulmonary Kaposi sarcoma and non-specific interstitial pneumonitis occurred in 4 patients each. In a multivariate regression model, predictors of PCP were typical chest X-ray and low CD4 count while purulent sputum predicted bacterial infection. The sensitivity of physicians and chest X-ray diagnosis was particularly low for PTB and bacterial infections. We conclude that chronic bacterial infection and Pneumocystis pneumonia are important differential diagnoses in HIV-infected, smear-negative PTB patients presenting with atypical chest X-ray. We therefore need to escalate the use of preventive and highly active antiretroviral (HAART) treatment in order to prevent a PCP epidemic.     

Defining and assessing the maximum number of visits patients should make to a health facility to obtain a diagnosis of pulmonary tuberculosis.

SETTING: All non-private hospitals in Malawi. OBJECTIVES: To determine 1) how many patients with pulmonary tuberculosis (PTB) exceed the maximum number of visits needed for registration as defined by the National Tuberculosis Control Programme, and 2) the factors associated with this delay. DESIGN: Cross-sectional study interviewing hospitalised patients with new smear-positive and smear-negative PTB. RESULTS: Of 380 patients with PTB admitted to the 44 hospitals visited between April and June 2002, 329 (212 smear-positive and 117 smear-negative PTB) were interviewed: 64 (30%) smear-positive PTB patients needed more than five visits, and 44 (37%) smear-negative PTB patients needed more than six visits before being registered and started on treatment. Factors associated with exceeding the maximum number of visits were the first visit being to a health centre, submission of > 1 set of sputum specimens, and > 1 course of antibiotics. The main consequence of exceeding the maximum number of visits was increased duration of cough and increased time spent at health facilities. CONCLUSION: One third of patients exceed the maximum number of visits for registration of PTB. The main consequence of this is an increased duration of cough and an increased time spent at health facilities. Ways to reduce this delay need to be found.     

2016年广东省涂阴培阳肺结核患者耐药情况分析

目的 了解广东省涂阴培阳肺结核患者的耐药情况。方法 收集广东省2016年1—12月32个结核病耐药监测点12323例临床确诊的初治涂阴肺结核患者作为研究对象,均进行了分枝杆菌培养检测,其中1224例阳性,涂阴培阳率为9.9%。经菌种鉴定,1177例(96.16%)为结核分枝杆菌复合群,47例(3.84%)为非结核分枝杆菌。对确定为结核分枝杆菌复合群的1177株菌株进行异烟肼(INH)、链霉素(Sm)、利福平(RFP)、乙胺丁醇(EMB)、卡那霉素(Km)、氧氟沙星(Ofx)、卷曲霉素(Cm)、丙硫异烟胺(Pto)、对氨基水杨酸(PAS)等9种药物的药物敏感性试验(简称“药敏试验”)。结果 12323例初治涂阴肺结核患者进行培养,涂阴培阳肺结核患者总耐药率为29.57%(348/1177),耐多药率为2.38%(28/1177),广泛耐药率为0.08%(1/1177),单耐药率为17.42%(205/1177),多耐药率为9.77%(115/1177)。男性耐多药率(2.94%,25/849)高于女性(0.91%,3/328),差异有统计学意义(χ ²=4.20,P=0.040)。多耐药谱有52种类型,其中耐INH+Sm者最多,占20.87%(24/115);其次为耐Sm+Km者(9.57%,11/115)。结论 广东省涂阴培阳肺结核患者有较高的耐药率,应加强监测与管理,减少耐药结核病的发生。     

Detection of Mycobacterium tuberculosis in bronchoalveolar lavage from patients with sputum smear-negative pulmonary tuberculosis using a polymerase chain reaction assay

Abstract The objective of this study was to evaluate the utility of a polymerase chain reaction (PCR) assay in detecting Mycobacterium tuberculosis in bronchoalveolar lavage (BAL) specimens of patients suspected of having active pulmonary tuberculosis (TB) but who were sputum smear-negative. Patients undergoing investigation for suspected pulmonary TB at the University Hospital, Kuala Lumpur, and who were sputum smear-negative underwent fibreoptic bronchoscopy and BAL. One portion of each lavage specimen was submitted for smear examination for acid-fast bacilli and mycobacterial culture and the other portion assayed by PCR for the presence of a 562-base pair DNA segment belonging to the insertion sequence IS986, unique to the M. tuberculosis complex. As controls, lavage specimens from patients with other lung lesions were also similarly tested. The PCR assay gave a positivity rate of 80.9% (55 of 68) compared with 8.8% of smear examination and 7.4% of culture for detecting M. tuberculosis in BAL specimens. The assay was positive in two of 45 BAL specimens from 35 control subjects. The PCR assay was more sensitive than smear and culture in detecting M. tuberculosis in BAL specimens of patients with sputum smear-negative pulmonary TB.     

Evaluation of outpatients with suspected pulmonary tuberculosis in a high HIV prevalence setting in Ethiopia: clinical,diagnostic and epidemiological characteristics

In a setting with a high prevalence of HIV we studied (i) the prevalence of pulmonary tuberculosis (PTB) and HIV; (ii) clinical and epidemiological characteristics of PTB; and (iii) the usefulness of standard procedures for diagnosing PTB. Of 509 consecutive outpatients evaluated on clinical suspicion of PTB in Addis Ababa, 33.0% were culture-verified as having PTB. PTB patients, non-TB patients and controls were HIV-1-positive in 57.1%, 38.5% and 8.3% of cases, respectively. Predictors for culture-verified PTB were age < 25 y, male gender and the presence of HIV and fever, whereas profound weight loss indicated HIV infection. Diagnosis of PTB based on clinical symptoms, sputum microscopy for acid-fast bacilli and chest radiography was sensitive (86.7%) but unspecific (64.1%). In HIV-positive patients both sensitivity and specificity were significantly lower (p < 0.05). HIV-related pulmonary infections are often misinterpreted as smear-negative PTB. HIV screening is therefore warranted not only in cases of verified TB but also as part of the diagnostic work-up in patients with respiratory symptoms suggestive of PTB. Also, increased awareness of, and improved diagnostic tools for, HIV-related pulmonary infections other than PTB are required, together with algorithms for patients with suspected PTB.     

How can detection of infectious tuberculosis be improved? Experience in the Somali region of Ethiopia.

In early 1999, 48% of pulmonary tuberculosis (PTB) cases detected in the Somali region of Ethiopia were smear-positive. Actions at the laboratory level and peer-review of smear-negative PTB diagnoses were proposed. Clinicians knew, but did not adhere to, the algorithm recommended by the National Tuberculosis Programme for these diagnoses, partly due to the costs involved to patients. Challenging clinicians, in a non-threatening way, to become more clinically rigorous proved successful, and the proportion of smear-positive PTB increased to 65%. Operational research is needed to assess the feasibility of these widely-recommended smear-negative PTB diagnosis guidelines.