Laboratory diagnosis of pulmonary tuberculosis in TB and HIV endemic settings and the contribution of real time PCR for M. tuberculosis in bronchoalveolar lavage fluid

Background Tuberculosis (TB) in Africa is increasing because of the human immunodeficiency virus (HIV) epidemic, and in HIV/AIDS patients it presents atypically. Pulmonary tuberculosis (PTB) in Africa is mainly diagnosed clinically, by chest radiograph or by sputum smear for acid fast bacilli (AFB). Methods We evaluated in 120 HIV‐infected patients with chest infection the diagnostic accuracy of AFB smear of sputum and bronchoalveolar lavage (BAL) fluid, sputum Mycobacterium tuberculosis (MTB) culture, real‐time PCR and MycoDot^® serological test, using MTB culture of BAL fluid as gold standard. We correlated PCR cycle threshold values (C_T) to the culture results. Retrospectively, we evaluated the development of active TB in patients with positive PCR but negative culture. Results Culture of BAL fluid identified 28 patients with PTB. Fifty‐six patients could not produce adequate sputum. Sputum AFB smear and the serological test had sensitivities of 66.7% and 0%, respectively. PCR with C_T 40 was positive in 73 patients, 27 of whom were also TB culture positive (96.4% sensitivity and 52.3% specificity of PCR). PCR with C_T 32 had sensitivity of 85.7% and specificity of 90.9% to diagnose PTB in BAL. No patients with positive PCR but negative culture developed active TB during 18 months follow‐up. Conclusion In these HIV‐infected patients, AFB smear and serology had very low sensitivities. PCR of BAL with C_T value 32 had improved specificity to diagnose active PTB. A prospective follow‐up study is warranted in TB/HIV endemic settings, applying real time PCR to both sputum and BAL.     

Response to empirical anti-tuberculosis treatment in patients with sputum smear-negative presumptive pulmonary tuberculosis

BACKGROUND: In many cases, physicians initiate anti-tuberculosis (TB) treatment based only on symptoms or radiographic findings without confirmation of pulmonary TB by acid-fast bacilli (AFB) smear. It has not been well known which clinical characteristics could be used as predictors for positive culture or real TB in patients with sputum smear-negative presumptive pulmonary TB. OBJECTIVE: We tried to elucidate treatment outcomes in patients with sputum smear-negative presumptive pulmonary TB and to find predictors of positive culture results. METHODS: We reviewed data of the patients who had been treated as presumptive TB with negative AFB smear on the basis of clinical and radiographic features from December 1998 to December 2000 at a university hospital in Korea. We reviewed medical records and radiographs of patients and analyzed possible predictors for positive culture. RESULTS: One hundred and one patients were enrolled. Among them, pulmonary TB was confirmed by culture in 32 patients (31%). Thirty-one (96.9%) out of 32 culture-positive patients showed clinical or radiographic improvement as did 50 (72.5%) out of 69 culture-negative patients. The predictor for a positive culture result is the presence of patchy consolidation in an initial radiograph (p = 0.025; OR 2.89; 95% CI 1.14-7.28). CONCLUSIONS: The empirical anti-TB treatment in patients with sputum smear-negative presumptive pulmonary TB was effective and adequate, especially presented with patchy consolidation in initial chest radiographs in Korea.     

Viability of stored sputum specimens for smear microscopy and culture.

A laboratory study was performed to determine how long sputum specimens from smear-positive tuberculosis patients can be stored at room temperature or in the refrigerator and retain a positive acid-fast bacilli (AFB) smear or a positive mycobacterial culture. Sputum samples from 30 patients were examined up to 4 weeks and samples from 13 patients examined up to 8 weeks. Provided samples had not dried out, all sputum smears remained AFB positive up to 4 and 8 weeks. In both patient groups, at 4 weeks 37-39% of specimens at room temperature grew mycobacteria compared with 54-67% of specimens stored in the refrigerator. These results have implications for tuberculosis programme policy.     

Completeness and timeliness of treatment initiation after laboratory diagnosis of tuberculosis in Gaborone, Botswana.

SETTING: Gaborone, the capital of Botswana. OBJECTIVE: To determine the time from positive sputum smear microscopy for acid-fast bacilli (AFB) to initiation of therapy, and to identify risk factors for delays. DESIGN: Retrospective cohort study of medical records and surveillance data for patients with positive smear microscopy and newly diagnosed tuberculosis (TB) from January to May 1997. Treatment delay was defined as more than 2 weeks from the first positive sputum smear to the initiation of TB treatment. RESULTS: Of 127 patients identified, 15 (11.8%) had treatment delay, 13 (10.2%) had an incomplete workup (only one smear performed) and were not registered for TB treatment, and six (4.5%) had two or more positive smears but were not registered for TB treatment. Risk factors for treatment delay or non-registration included TB patients who had been diagnosed in a hospital outpatient setting vs. a clinic (RR 2.9, 95% CI 1.2-3.6, P = 0.02), or in a high volume vs. low volume clinic (RR 2.2, 95% CI 1.2-5.3, P = 0.01). CONCLUSION: More than a quarter of the smear-positive TB patients identified had treatment delay or no evidence of treatment initiation. Proper monitoring of laboratory sputum results and suspect TB patient registers could potentially reduce treatment delays and patient loss.     

Number of negative acid-fast smears needed to adequately assess infectivity of patients with pulmonary tuberculosis

STUDY OBJECTIVES: To investigate the relationship between the number of negative acid-fast bacilli (AFB) smear results and infectivity of pulmonary tuberculosis (TB). DESIGN: Retrospective analysis. METHODS AND SUBJECTS: We examined 122 index cases in Harris County, TX, reported in 1998 and 1999. All cases had only negative AFB smear results during the infectious period and were categorized in two groups: group A consisted of cases with only one or two sputum specimens collected and processed, and group B consisted of cases with at least three sputum specimens or at least one bronchoscopic specimen. Tuberculin skin test (TST) results of contacts were ascertained from the results of contact investigations performed by the City of Houston Department of Health and Human Services, Tuberculosis Control Division. Univariate and multivariate analyses were done to explore index case and contact attributes associated with tuberculosis (TB) transmission using positive TST results of contacts as a measure of recent transmission. RESULTS: We found male gender and younger age of index cases along with Hispanic ethnicity of contacts to be independently associated with positive TST results, while younger contacts were less likely to be TST positive. Smear category of the index case (group A vs group B) was not independently associated with transmission. We also found that the first two sputum specimens in cases where three or more were performed yielded 90% of all positive culture results for Mycobacterium tuberculosis (MTB). CONCLUSIONS: We conclude that two sputum specimens negative for AFB stain are adequate for both assessing infectivity and for isolating MTB from patients with pulmonary TB.     

The validity of acid-fast smears of gastric aspirates as an indicator of pulmonary tuberculosis.

SETTING: A tuberculosis referral hospital in Canada. OBJECTIVE: To determine the validity of acid-fast (AFB) smears of gastric aspirates (GA) in the diagnosis of pulmonary tuberculosis, and to assess the prevalence of nontuberculous mycobacteria (NTM) in GA isolates from such patients. DESIGN: A retrospective case review of our experience with AFB smears (Kinyoun) and cultures of GA and sputum over a 3-year period. RESULTS: From 1994 to 1996 inclusive, 1155 GA were performed in 889 patients. Mycobacteria were cultured from 109 (9%) GA. Thirteen of these were positive on smear (sensitivity 19%). All GA that were positive on smear were culture positive for Mycobacterium tuberculosis. There were no false positive smears (specificity 100%). The sensitivity and specificity of the sputum smear were 45% and 99%, respectively. Of the 96 culture positive, smear negative GA, 54 grew M. tuberculosis and 42 grew an NTM. Of 13 patients who had sputum and GA studied coincidentally, and in whom the sputum was both smear and culture positive, the GA culture was positive in 13 and the smear was positive in eight (66%). CONCLUSION: AFB smear of GA is a relatively insensitive but highly specific indicator of pulmonary tuberculosis warranting institution of antituberculosis treatment. Gastric AFB smear positivity appears to reflect a high bacillary burden within the respiratory tract.     

Identifying pulmonary tuberculosis in patients with negative sputum smear results

BACKGROUND: Clinicians need to decide whether to begin empiric therapy for patients who are suspected of having tuberculosis (TB) but have negative sputum smear results. Culture results may take weeks, and delaying treatment may allow further transmission of disease. Study objective: To identify the clinical, demographic, and radiographic characteristics that identify smear-negative patients who have TB, and to create a TB prediction rule. DESIGN: Retrospective chart review. SETTING: University-affiliated public hospital in San Francisco, CA, between 1993 and 1998. PATIENTS: Forty-seven patients with TB and 141 control patients who were hospitalized with a suspicion of pulmonary TB; all had negative sputum smear results. Measurements and results: Demographic, clinical, and radiographic variables were determined by chart review. In multivariate analysis, a positive tuberculin skin test result (odds ratio [OR], 4.8; 95% confidence interval [CI], 2.0 to 11.9) was independently associated with an increased risk of a positive TB culture finding. A radiographic pattern not typical of pulmonary tuberculosis (OR, 0.3; 95% CI, 0.1 to 0.7) and expectoration with cough (OR, 0.3; 95% CI, 0.1 to 0.6) were predictive of a decreased risk. An interaction between HIV seropositivity and mediastinal lymphadenopathy on the chest radiograph was also associated with a positive TB culture result (OR, 7.2; 95% CI, 1.4 to 36.0). The TB prediction score (TPS) was created with widely ranging likelihood ratios that could affect the posterior probability of TB by 30-fold. CONCLUSION: The TPS put into context with the overall prevalence of TB in a given area may help clinicians decide if a patient with negative sputum smear results should start empiric antituberculous therapy or wait for culture results. These results need prospective validation.     

Clinical characteristics and treatment response among patients with multidrug-resistant tuberculosis: a retrospective study

BACKGROUND: This retrospective study was conducted to evaluate the characteristics and therapeutic response among patients with multidrug-resistant tuberculosis (MDR TB). METHODS: One hundred subjects with isolates resistant to isoniazid and rifampicin were included over a three-year period (1997-1999). There were 82% males with a mean age of 36 years, mean duration of symptoms of 29 months, and a previous history of tuberculosis in 85% (pulmonary 96% and extrapulmonary 4%). RESULTS: HIV ELISA test was positive in two out of 28 (7%) patients while diabetes was diagnosed in 16 percent. Mean time to diagnose MDR TB was 5.5 months. Subjects had received a mean of 3.2 anti-TB drugs before the diagnosis of MDR TB was made. Forty-five patients were lost to follow-up. The rest had a median follow-up of 13.5 months (range 1-37 months). Follow-up AFB smear and culture results were available in 49 out of 55 and 26 out of 55 patients, respectively. Sputum smear became negative for AFB in 26 out of 49 (53%) and culture converison occurred in 16 out of 26 (61.5%) patients. Clinical and radiological response was noted in 31 (56%) and 13 (32.5%) out of 40 patients respectively. A mean of 5.5 drugs was used in those who achieved sputum conversion. Combination therapy containing ofloxacin in the regimen was noted to have a favourable response. CONCLUSION: Only a limited number of patients with MDR tuberculosis have a favourable response.     

对肺结核可疑者采用症状查痰法提高患者发现率

目的探讨更全面的发现肺结核病例的检查诊断程序。方法在采用通用的胸透筛查法发现肺结核患者的基础上，采用症状查痰法，对有症状且≥3周者，直接做痰结核分枝杆菌检查，并拍摄X线胸片，对按胸透筛查法和症状查痰法发现的患者进行比较；对肺结核诊断程序改进后的结核病患者的发现情况进行分析。结果采用症状查痰法发现活动性肺结核新病例900例，比胸透筛查法多发现活动性肺结核患者73例，患者发现率提高8．8％(73／827)；发现涂阳肺结核病例262例，比胸透筛查法多发现活动性肺结核患者30例，患者发现率提高12．9％(30／232)；培养阳性肺结核病例360例，比胸透筛查法多发现患者63例，患者发现率提高21．2％(63／297)。症状查痰法发现新病例的细菌学检查阳性者的比例高于胸透筛查法，胸透筛查法发现新病例中，涂片阳性者占28．1％(232／827)，痰菌培养阳性者占35．9％(297／827)；而症状查痰法发现新病例中，涂片阳性者占29．1％(262／900)，痰菌培养阳性者占40．0％(360／900)。症状查痰法多检出的活动性肺结核患者73例中，涂阳和菌阳患者的比例均很高，分别为41．1％(30／73)和86．3％(63／73)，较胸透筛查法的检出涂阳比例(28．1％)和菌阳比例(35．9％)高。结论采用症状查痰法比胸透筛查法发现的活动性肺结核患者增加，特别是菌阳肺结核患者的发现率增加21．2％，使这些患者得到及时诊断，有利于结核病传染源的控制。     

Value of smear and PCR in bronchoalveolar lavage fluid in culture positive pulmonary tuberculosis.

At present, further investigations are needed in patients with suspected pulmonary tuberculosis (TB) and either negative sputum smear or without sputum. The aim of the present study was to analyse the yield of bronchoalveolar lavage fluid (BALF) smear and PCR in patients with confirmed pulmonary TB. Patients with a positive culture for Mycobacterium tuberculosis complex in sputum or BALF were analysed over 5 yrs. In total, 90 out of 230 (39%) patients with culture-positive pulmonary TB had a positive sputum smear, and 120 patients underwent bronchoscopy. BALF smear was positive in 56 (47%), BALF PCR in 93 (78%) patients, and BALF smear and/or PCR was positive in 83%. In total, 71 patients who underwent bronchoscopy and had complete clinical records were further analysed. BALF (smear or Mycobacterium tuberculosis complex-PCR) allowed a rapid diagnosis in 10 (59%) out of 17 patients who had a negative sputum smear, and 49 (91%) out of 54 patients without sputum production. Of these 71 patients, 12 (17%) were only culture positive. Rapid diagnosis of pulmonary TB by smear and/or PCR was made in 190 out of 210 patients (90%) in sputum or BALF. In conclusion, combined use of bronchoalveolar lavage fluid smear and Mycobacterium tuberculosis complex-PCR has a good diagnostic yield in patients with sputum smear-negative tuberculosis or without sputum production.     

Role of Gene Xpert in smear negative pulmonary tuberculosis

BackgroundTuberculosis is a major health problem contributing to significant morbidity and mortality. Early diagnosis and treatment is the key for TB control. Sputum microscopy is a rapid and inexpensive test but due to low and variable sensitivity, many cases can be missed. Culture is considered to be the gold standard but is time consuming. Gene Xpert is a novel and rapid cartridge based nucleic acid amplification test (CBNAAT) that can be used for prompt diagnosis.AimTo compare the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of Gene Xpert with culture in diagnosing tuberculosis in sputum smear negative patients.MethodsThe study is a prospective observational study conducted from December 2017 to January 2019 on 189 patients, who were sputum smear negative but had signs and symptoms suggestive of tuberculosis. Their respiratory samples were taken (either sputum or bronchoalveolar lavage) and sent for Gene Xpert. The results were compared with culture, which was taken as the gold standard, and diagnostic accuracy was assessed.ResultA total of 189 patients were included in the study. In 25 patients sputum was taken and in 164 patients BAL was taken (which included 22 patients in whom sputum Gene Xpert was negative but there was high clinical suspicion of tuberculosis). The sensitivity, specificity, PPV and NPV of Gene Xpert in diagnosing smear negative pulmonary tuberculosis was found to be 96.3%, 81.3%, 87.5% and 94.2% respectively.ConclusionGene Xpert can be used as a rapid diagnostic tool in patients who are sputum smear negative but have clinical features highly suggestive of tuberculosis. It additionally helps in detecting rifampicin resistance. But every Gene Xpert positive case does not necessarily mean an active disease, therefore, past history of tuberculosis along with radiological signs of disease activity are to be considered. In case of negative Gene Xpert but high clinico-radiological suspicion of TB, patients should be followed up on regular intervals, while awaiting their culture.     

Unexpected pulmonary involvement in extrapulmonary tuberculosis patients

BACKGROUND: This study aimed to assess the utility of sputum examinations and chest radiographs (CXRs) in patients with extrapulmonary tuberculosis (XPTB) to detect pulmonary involvement of tuberculosis (TB). METHODS: We studied 72 XPTB patients who were managed through the TB Program, King County, WA, from January 2003 through November 2004. RESULTS: The two most common sites of XPTB were the lymph nodes (36 [50%]) and pleura (12 [17%]). Thirty-five of 72 XPTB patients (49%) had abnormal CXR findings. Sputum was not obtained from 15 patients despite sputum induction. Of the 57 patients from whom sputum was collected, 30 (53%) had abnormal CXR findings, 5 (9%) had sputum smears that were positive for acid-fast bacilli, and 12 (21%) had sputum cultures that were positive for Mycobacterium tuberculosis. Weight loss was significantly associated with positive sputum culture findings in a multivariate analysis (odds ratio, 4.3; 95% confidence interval, 1.01 to 18.72; p = 0.049). There was no significant difference in the occurrence of positive sputum culture results between patients with abnormal CXR findings and those with normal CXR findings (7 of 30 patients [23%] vs 5 of 27 patients [19%], respectively; p = 0.656). Of 24 HIV-negative XPTB patients with normal CXR findings, 2 patients (8%) had positive sputum culture findings. CONCLUSIONS: CXR results did not reliably differentiate XPTB patients with and without positive sputum culture findings. Some XPTB patients had positive sputum culture results despite normal CXR findings and negative HIV status. Weight loss in XPTB patients was associated with positive sputum culture results. Sputum examinations in XPTB patients, regardless of the CXR results, may identify potentially infectious cases of TB.     

Diagnostic value of gastric aspirate smear and polymerase chain reaction in smear-negative pulmonary tuberculosis

OBJECTIVE: The aim of this study was to determine the validity of acid-fast bacilli (AFB) smear and polymerase chain reaction (PCR) from gastric aspirates for the diagnosis of smear-negative pulmonary tuberculosis. METHODOLOGY: A cross-sectional study was conducted in a university hospital. One hundred and nine patients with suspected pulmonary tuberculosis in whom either sputum smears were negative or who were not producing sputum were recruited to the study. All patients underwent gastric aspiration after an overnight fast followed by standard fibreoptic bronchoscopy. Specimens were subjected to AFB smear, culture, and pathological examination. PCR was performed on culture filtrate after 1 week of incubation. RESULTS: Eight patients did not complete the follow-up schedule. Of the 101 patients with final outcomes, a diagnosis of pulmonary tuberculosis from microbiological evidence was established in 54 patients. The gastric aspirate smear, PCR, or either one of them was positive in 34, 30, and 39 tuberculosis patients, respectively. There were 13 false positive smears from 47 non-tuberculosis patients, with five resulting from non-tuberculous mycobacteria (NTM). The PCR was falsely positive in eight patients, five of whom had previous histories of tuberculosis. The overall sensitivity, specificity, positive predictive value, and negative predictive value of gastric aspirate examination by combined smear and PCR were 72, 58, 66, and 64%, respectively. CONCLUSIONS: Gastric aspiration is a useful tool for the diagnosis of smear-negative pulmonary tuberculosis warranting institution of antituberculosis treatment. Interpretation of the results should be cautious in those who have had tuberculosis in the past or who have been at risk for acquisition of NTM.     

New recommendations for duration of respiratory isolation based on time to detect Mycobacterium tuberculosis in liquid culture.

It was hypothesised that the time to detect Mycobacterium tuberculosis in liquid culture of sputum from patients with pulmonary tuberculosis may be a better indicator for the duration of respiratory isolation than sputum smear status. Pre-treatment and during-treatment sputum acid-fast bacilli (AFB) smear and culture results were reviewed in 284 patients with pulmonary tuberculosis. The time to detect M. tuberculosis in liquid culture (TTD-TB) was the number of days from inoculation of the Mycobacterial Growth Indicator Tube to culture detection and visualisation of AFB. The median (interquartile range) TTD-TB for smear group 0 (no bacilli seen) was 14 (12-20) days. This value was used as the standard at which release from isolation could be permitted. In smear group 4 (>9 AFB per high-power field (hpf) in sputum specimens before treatment) patients, the TTD-TB exceeded 14 days after a median of 25 days of treatment. The current authors recommend that patients in smear groups 1 and 2 (1-9 AFB per 100 hpf and 1-9 AFB per 10 hpf in sputum specimens before treatment, respectively) receive treatment in respiratory isolation for 7 days, provided the risk of drug resistance is low. Smear group 3 (1-9 AFB per hpf) and 4 patients should receive treatment in respiratory isolation for 14 and 25 days, respectively. These criteria would have reduced the duration of respiratory isolation by 1,516 days in the 143 study participants with sputum smear-positive pulmonary tuberculosis. Provided clinical and radiographical criteria are satisfactory, use of the time to detect Mycobacterium tuberculosis in liquid culture could enable the duration of respiratory isolation to be predicted from the pre-treatment sputum smear grade. The recommendations enable isolation to end well before sputum becomes smear negative, with considerable benefits to patients and healthcare providers.     

Health-seeking behaviour among adults with prolonged cough in Vietnam

Objective To assess health‐seeking behaviour among adults with prolonged cough in a population‐based, nationally representative sample in Vietnam. Methods Cross‐sectional survey conducted from September 2006 to July 2007. All inhabitants aged ≥15 years were invited for screening for cough, history of tuberculosis (TB) treatment and chest X‐ray (CXR) examination. TB suspects, defined as any survey participant with CXR abnormalities consistent with TB, or productive cough for more than 2 weeks or TB treatment either currently or in the preceding 2 years submitted sputum specimens for smear examination and culture and provided information on health‐seeking behaviour in an in‐depth interview. Results Of 94 179 persons participating in the survey, 4.6% had prolonged productive cough. Forty‐four percentage of those had sought health care and reported pharmacies (35%), commune health posts (29%), public hospitals (24%) and private physicians (10%) as first point of contact. Only 7% had undergone sputum smear examination. Of TB suspects with prolonged productive cough, 2.9% were diagnosed with TB; 10.2% of these reported smear and 21.9% reported X‐ray examination when visiting a health care facility. The average patient delay was 4.1 weeks (95% CI: 3.9–4.4) among cough suspects and 4.0 weeks (95% CI: 3.1–4.9) among TB cases. Conclusions In this Vietnamese survey, nearly half of persons with cough for more than 2 weeks had visited a health care provider. The commonest first health facility contacted was the pharmacy. Sputum smears were rarely examined, except in the provincial TB hospital. Our findings highlight the need to improve diagnostic practices by retraining health staff on the performance of sputum examination for TB suspects.     

Can serial qualitative polymerase chain reaction monitoring predict outcome of pulmonary tuberculosis treatment?

BACKGROUND: The aim of this study was to assess the use of qualitative one-tube nested polymerase chain reaction (PCR) for monitoring the treatment response in smear-positive pulmonary tuberculosis, and the factors determining the negative conversion of sputum smear, culture, and PCR during treatment. METHODOLOGY: A total of 53 patients receiving a standard short course of chemotherapy with 24 months follow-up period after treatment cessation were included in the study. Sputum specimens were collected serially for smear, culture, and PCR until the treatment was complete. RESULTS: The conversion rate for sputum culture, smear, and PCR at 8 weeks after treatment were 84.9, 58.5, and 47.1%, and at 16 weeks of treatment were 100, 88.7, and 79.2%, respectively. At the end of the treatment period, there were four PCR persisters, one of whom had disease relapse. Only cavitary disease had an influence over the negative conversion of the smear and PCR at 8 weeks (RR 3.5, 95% CI 1.04-11.95, P=0.04 for smear; RR 5.06, 95% CI 1.196-21.42, P=0.03 for PCR). CONCLUSION: Qualitative PCR was not useful for monitoring therapy in smear-positive pulmonary tuberculosis. Mycobacterium DNA was cleared slowly in cavitary disease. The PCR may be performed at the time of treatment cessation to identify those with potential for disease relapse.     

The value of bronchial lavage in patients with radiologically suggestive pulmonary tuberculosis with no sputum production and gastric lavage smear negativity

We assessed whether acid-fast bacilli (AFB) investigation in bronchial lavage (BL) contributes to diagnosis in patients with gastric lavage smear negative and radiologically suggestive of pulmonary tuberculosis. Eighty-three patients were recruited for the study, five cases were excluded due to diagnosis of inactive disease or non-tuberculosis disease. The remaining 78 patients were evaluated. All patients were unable to expectorate sputum and their gastric lavages were negative for AFB. BL was performed for the detection of Mycobacterium tuberculosis in all patients. Bronchial lavage smear were positive in 15.4%(12 patients). BL culture positivity was 58.3%(42 patients) and gastric lavage culture positivity was 33.3%(26 patients). Eighteen cases had both gastric lavage and BL culture positivity. BL culture was positive in 24 cases who had gastric lavage culture negativity. We suggest that in cases who do not produce sputum and whose gastric lavage smears are negative; BL should be performed for diagnosis of pulmonary tuberculosis.     

263例住院肺结核患者痰涂片抗酸杆菌阳性检出分析

目的了解住院肺结核患者痰涂片抗酸杆菌（AFB）阳性检出特征,为肺结核诊断提供可靠依据。方法对263例住院肺结核患者痰标本直接厚涂片AFB检查,并对涂阳患者进行I豳床分析。结果发现涂片阳性肺结核患者95例,阳性率36．1％。其中AFB（±）7例（7．4％）、AFB（1＋）36例（37．9％）、AFB（2＋）20例（21．0％）、AFB（3＋）13例（13．7％）、AFB（4＋）19例（20．0％）。三个痰标本首次涂片阳性率为65．3％（62／95）,清晨痰标本阳性检出率为61．8％（84／136）,涂阳患者三种不同痰标本和不同送检次数在AFB阳性检出上均有统计学意义（P〈0．01）。与涂阴肺结核比较,涂阳肺结核患者咳嗽、咯血、发热、空洞形成和病灶≥2个肺野等比例分别高达97．9％、41．1％、54．7％、48．4％和82．1％,存在显著性差异（P〈0．05）。结论留取合格痰标本,认真涂片检查,提高痰标本阳性检出率,痰涂片检查符合我国国情,是实施结核病控制项目DOTS策略的关键之一。     

Outcomes of patients with multidrug-resistant pulmonary tuberculosis treated with ofloxacin/levofloxacin-containing regimens

OBJECTIVE: To analyze outcomes of patients with multidrug-resistant tuberculosis (MDR-TB) treated with ofloxacin/levofloxacin-containing regimens. MATERIALS AND METHODS: From February 1990 through June 1997, 63 MDR-TB patients (with bacillary resistance to at least isoniazid and rifampin in vitro) were analyzed retrospectively. Twenty-two patients (34.9%) had had no previous antituberculosis chemotherapy. Each patient received either ofloxacin (53) or levofloxacin (10) even though 13 patients had bacilli resistant to ofloxacin in vitro. The other accompanying drugs mainly included aminoglycosides, cycloserine, ethionamide/prothionamide, and pyrazinamide. Sputum smear and culture examinations for acid-fast bacilli (AFB) were performed monthly for the initial 6 months and then at 2- to 3-month intervals until the end of treatment. Comparison was made between clinical successes and failures using univariate and multiple logistic regression analyses for the following variables: age, sex, presence of cavitation, extent of disease, sputum smear positivity, in vitro resistance to ofloxacin, in vitro resistance to streptomycin and/or ethambutol, treatment adherence, and the number of drugs per regimen. RESULTS: Fifty-one patients (81.0%) were cured, nine patients (14.3%) failed, and three patients (4.7%) died. For the entire group, the mean duration of treatment was 14.0 months, and the mean number of drugs was 4.7. Mean durations of chemotherapy in successful and failed patients were 14.5 and 14.2 months, respectively. Mean time for sputum smear and culture conversions were 1.7 and 2.1 months, respectively. Only cavitation, resistance to ofloxacin, and poor adherence were found to be variables independently associated with adverse outcomes (p < 0.05; odds ratios = 15.9, 13.5, 12.8, respectively). Negative sputum cultures after 2 and 3 months of therapy were 100% predictive of cure. Positive sputum cultures after 2 and 3 months were 52.3% and 84.6% predictive of failure, respectively. One patient (2.1%) relapsed after apparent cure. Twenty-five patients experienced adverse drug reactions, but only 12 of them needed drug modifications. CONCLUSION: Most MDR-TB patients can be treated effectively with ofloxacin/levofloxacin-containing regimens. Presence of cavitation, resistance to ofloxacin in vitro, and poor adherence to therapy portend treatment failure. Monitoring monthly sputum culture for AFB in the initial months of chemotherapy helps predict clinical outcomes.     

Integration of microscopy and serodiagnostic tests to screen for active tuberculosis.

SETTING: University of California San Diego Medical Center, USA. OBJECTIVE: To create a simple screening strategy for tuberculosis (TB) that includes antibody detection assays to improve the accuracy of microscopic examination of sputum for acid-fast bacilli (AFB smear). METHODS: Serum samples were obtained from 190 patients suspected of having active TB. TB diagnosis was established by Mycobacterium tuberculosis culture. HIV status was determined by commercial serologic tests. IgG antibody levels were measured by ELISA using purified M. tuberculosis antigens. Data from 130 randomly selected patients were used to develop a screening strategy; data from the remaining 60 patients were used for validation. RESULTS: AFB smear had 70% sensitivity and 88% specificity. In algorithms integrating single or multi-antigen ELISA with AFB smear and HIV results, the sensitivity improved over each test alone. The algorithm that included a four-antigen ELISA (38 kDa antigen, lipoarabinomannan, MPT-64 and glutamine synthase) had a sensitivity of 93% and a specificity of 76%. Compared to AFB smear, the sensitivity of the algorithm was significantly higher, while the specificity was not statistically different. CONCLUSION: This study demonstrates that a screening strategy can be created by integrating multi-antigen ELISA with AFB smear and HIV testing.