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.     

Treatment results of DOTS in 1797 Sudanese tuberculosis patients with or without HIV co-infection.

SETTING: Consecutive new tuberculosis (TB) patients, from eight states in Sudan, who had never been previously treated for as much as 1 month between 1998 and 2000. OBJECTIVE: To determine the impact of human immunodeficiency virus (HIV) co-infection on tuberculosis treatment outcome. DESIGN: All patients presenting with symptoms suggestive of tuberculosis underwent sputum microscopy for acid-fast bacilli (AFB). Treatment is free of charge, and directly observed for all smear-positive patients. Treatment outcomes were those defined by the World Health Organization. All patients were tested anonymously for human immunodeficiency virus (HIV) using the Bionor test. RESULTS: Of 10 494 patients suspected of TB and referred for sputum microscopy, 1797 were TB cases; 983 had smear-positive pulmonary tuberculosis, 521 smear-negative pulmonary tuberculosis, and 293 extra-pulmonary tuberculosis. Smear-positive cases showed a cure rate of 77.2% and a failure rate of 1%. Smear-negative and extra-pulmonary patients had a completion rate of 79.4%. Cure rates for the smear-positive cases were 68.3% for HIV-positive and 77.6% for HIV-negative patients (P = 0.164). Case fatality was significantly higher among HIV-positive (12%) than among HIV-negative cases (1.8%) (OR 7.7, 95% CI 3.51-16.8). CONCLUSION: To date, a relatively low proportion of tuberculosis patients in Sudan also have HIV infection. These patients are substantially more likely to die while on treatment for their tuberculosis, a fact that underlines their need for more comprehensive care if their lives are to be prolonged. In addition, every effort is required to diminish the transmission of HIV infection to prevent the tragedy this infection represents to the community.     

Risk factors for tuberculosis infection in sub-Saharan Africa: a contact study in The Gambia

Few studies have investigated the risk factors for tuberculosis (TB) infection in highly endemic countries. We conducted a household study in The Gambia, in which a tuberculin skin test (TST) was performed in members of the households of 315 smear-positive pulmonary TB cases and 305 community control subjects. The risk of being TST positive (10 mm or more) was higher in contacts of cases than in contacts of control subjects. It increased with age, male sex, and duration of stay in the household but was not associated with the presence of a bacille de Calmette-Guérin scar. Within the households of the TB cases, the risk of TST positivity was higher in males and was increased with age, social proximity to the case, and the radiologic extent of the disease in the case's chest X-ray. Adjusting on these, the risk of TST positivity was higher in first-degree relatives compared with more distant relatives and nongenetically related household members, but the effect was not statistically significant. In highly endemic areas, the risk of TB infection in contacts of TB infectious cases is associated with age, sex, intensity of exposure to the case, and severity of disease in the case, but it is possible that genetic factors contribute to the susceptibility to Mycobacterium tuberculosis infection.     

The effect of bacille Calmette-Guérin vaccination at birth on tuberculin skin test reactivity in Ugandan children.

SETTING: In Uganda, bacille-Calmette Guerin (BCG) vaccination coverage at birth is between 82 and 84%. OBJECTIVE: To evaluate the effect of neonatal BCG vaccination on tuberculin skin test positivity in Ugandan children exposed to infectious cases. DESIGN: As part of an ongoing prevalence study of household contacts of new tuberculosis cases, 365 children were evaluated to determine if BCG vaccination at birth had an impact on tuberculin skin testing. The children were classified as contacts (179) and non-contacts (186) depending on the presence of a sputum acid-fast bacilli (AFB) smear-positive adult tuberculosis case in the household. RESULTS: Regardless of prior BCG vaccination, children exposed to a smear-positive adult were more likely to have a positive skin test (purified protein derivative >5mm) (68% versus 36%, P < 0.01). BCG-vaccinated children below 1 year of age without a known household contact with active tuberculosis had a lower frequency of tuberculin skin reactions (29%) compared to their counterparts in the contact households (65%, P = 0.031). CONCLUSION: BCG vaccination at birth had no important effect on the interpretation of the tuberculin skin test reactivity in this group of Ugandan children. The tuberculin skin test remains a valuable tool for the evaluation of household contacts and suspected cases of tuberculosis in BCG-vaccinated children.     

Risk factors for transmission of Mycobacterium tuberculosis from HIV-infected tuberculosis patients, Botswana.

OBJECTIVE: To identify risk factors for transmission of Mycobacterium tuberculosis from patients with tuberculosis and human immunodeficiency virus (HIV) infection in Botswana. DESIGN: Transmission was studied in 210 children aged <10 years (contacts) of unknown HIV status exposed to 51 adults with tuberculosis (index cases), including 41/49 (83.7%) with HIV infection. METHODS: Data collected on index cases included demographics, clinical and social characteristics, sputum, HIV, and CD4 lymphocyte results. Tuberculin skin testing was performed on contacts, and their parent or guardian was interviewed. A positive test was defined as > or = 10 mm induration. Skin test results were compared with results obtained from a population survey of children of similar age from the same community. RESULTS: A positive skin test was found in 12.1% of exposed children compared with 6.2% in the community (P = 0.005). Of the infected children, 22 (78.6%) were contacts of a close female relative. The risk of transmission increased with the degree of sputum smear positivity for acid-fast bacilli among female index cases (10.8% if smear 0+, 9.3% if smear 1+,29.4% if smear 2+, 44% if smear 3+, P < 0.001). In multivariate analysis, severe immunodeficiency (CD4 lymphocyte count <200 cells/mm3) among HIV-infected index cases was protective against transmission (OR 0.08, 95%CI 0.01-0.5, P = 0.006). CONCLUSION: The intensity of exposure to tuberculosis patients and the degree of sputum smear positivity for acid-fast bacilli remain important risk factors for transmission of M. tuberculosis during the era of HIV. However, tuberculosis patients with advanced AIDS may be less infectious than patients in earlier stages of AIDS.     

Delayed tuberculosis diagnosis and tuberculosis transmission.

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

武汉市635例初治涂阳肺结核患者家庭接触者肺结核发病情况分析

搜集2015年1月至2017年12月武汉市肺科医院住院的635例初治涂阳肺结核患者的临床资料,筛查1242名家庭接触者活动性肺结核的检出率。家庭接触者中活动性肺结核检出率为1.69%(21/1242)。家庭接触者中配偶、父母、子女或其他亲属活动性肺结核检出率分别为 1.51%(7/464)、3.66%(9/246)和0.94%(5/532),父母的肺结核检出率最高,差异有统计学意义(χ ²=7.036,P=0.008)。荧光染色分枝杆菌阳性、+、++、+++、++++患者家庭接触者检出率分别为0.60%(2/334)、0.50%(2/401)、1.11%(3/271)、4.32%(6/139)、8.25%(8/97),差异有统计学意义(χ ²=37.232,P=0.000)。初治涂阳肺结核并发气管支气管结核患者的家庭接触者活动性肺结核检出率为3.01%(10/332)。当初治涂阳肺结核患者痰菌量大、并发气管支气管结核,或接触者为患者父母则更易被传染。     

Diagnostic yield of repeated smear microscopy examinations among patients suspected of pulmonary TB in Shandong province of China.

OBJECTIVES: To analyse the yield of five repeated smear microscopy examinations for the diagnosis of smear-positive pulmonary tuberculosis (TB). METHODS: Patients with respiratory symptoms and abnormal chest X-rays provided five spontaneous sputum samples for acid-fast bacilli (AFB) smear microscopy in one of nine county laboratories. RESULTS: Of 9302 patients with respiratory symptoms and abnormal X-rays, 6437 (69%) had at least one smear-positive sputum. Of these, 84.5% were diagnosed on the first smear, 96.7% on the first two smears, and 99.9% on the first three sputum smears. The fourth and fifth sputum smears yielded only seven additional cases (0.1%). CONCLUSIONS: Smear microscopy examination of two spontaneous sputum specimens is the most efficient, and three sputum smear examinations provide a diagnosis in almost all cases.     

A rapid survey to determine the prevalence of smear-positive tuberculosis in Addis Ababa.

SETTING: Four kebeles (lowest administrative units) in a typical district of Addis Ababa, Ethiopia. OBJECTIVE: To determine the prevalence of smear-positive pulmonary tuberculosis (TB) in an adult population by using a screening questionnaire and sputum examination. DESIGN: A house-to-house visit was conducted. All those 14 years of age and above were screened for the presence of symptoms. Three sputum samples were collected from persons who had symptoms for acid-fast bacilli (AFB) examination. RESULTS: A total of 12,149 individuals were screened, of whom 173 had symptoms suggestive of TB. Twenty-three were positive for AFB (189/100,000, 95% CI 112-267). No association was observed between smear positivity and socio-demographic factors. Only two of the 23 patients were on anti-tuberculosis treatment (8.7%, 95% CI 1.5-29.5). CONCLUSION: This simple and cost-effective method provides a fairly realistic estimate of the prevalence of TB. Thus with further development of the method it can be used to monitor the progress of TB programmes in resource-poor settings.     

A minimum 5.0 ml of sputum improves the sensitivity of acid-fast smear for Mycobacterium tuberculosis

Detection of acid-fast bacilli (AFB) by sputum smear supports treatment decisions with pulmonary tuberculosis (TB), but smear sensitivity for Mycobacterium tuberculosis is only approximately 45 to 75%. In an effort to increase sensitivity, smears were prepared using a minimum sputum volume of 5.0 ml. Sensitivity of smears during a 39-mo period (n = 1,849) using >/= 5.0 ml of sputum was 92. 0%, significantly greater (p < 0.001) than a sensitivity of 72.5% in a previous 24-mo period (n = 3,486) when all specimens were processed regardless of volume. All new cases of TB (n = 18) were smear-positive with >/= 5.0 ml of sputum before treatment, and all were receiving antituberculosis drugs at hospital discharge. In contrast, significantly fewer new cases of TB (14 of 26, p = 0.002) were positive before treatment when smears were prepared using sputum of any volume, and significantly fewer of these new TB cases (18 of 26, p = 0.03) were receiving treatment at hospital discharge. The eight cases without treatment were smear-negative. These results indicate that acid-fast smear using >/= 5.0 ml of sputum increases sensitivity for M. tuberculosis and accelerates treatment of TB.     

Infection and disease among household contacts of patients with multidrug-resistant tuberculosis.

SETTING: Urban public teaching and referral hospital in Espirito Santo, Brazil. OBJECTIVE: To assess whether rates of infection and progression to active tuberculosis (TB) differed between household contacts of patients with multidrug-resistant (MDR) and drug susceptible (DS) pulmonary tuberculosis. DESIGN: Household contacts were assessed for evidence of TB infection and disease by purified protein derivative (PPD) skin testing, physical examination, chest X-ray, and sputum smear and culture. RESULTS: Among 133 close contacts of patients with MDR-TB, 44% were PPD-positive (> or =10 mm) compared to 37% of 231 contacts of the DS-TB cases (P = 0.18, chi2 test, OR 1.2, 95%CI 0.8-2). In a multivariate logistic regression analysis, after allowance for between-household variation in PPD responses, PPD positivity among household contacts of patients with MDR-TB remained comparable to PPD positivity in contacts of patients with DS-TB (OR 2.1, 95%CI 0.7-6.5). Respectively six (4%) and 11 (4%) contacts of the MDR- and DS-TB cases were found to have active TB at the time of initial evaluation or during follow-up (P = 0.78, chi2 test). Five of six contacts of MDR-TB cases and nine of nine contacts of DS-TB cases who developed TB, and for whom drug susceptibility test results were available, had the same bacterial susceptibility profiles as their index cases. DNA fingerprinting analysis of Mycobacterium tuberculosis isolates was identical between household contacts with active TB and the index MDR or DS-TB case for all 14 pairs compared. CONCLUSION: Our data suggest that the prevalence of tuberculous infection and progression to active TB among household contacts exposed to DS and MDR-TB cases is comparable, despite a longer duration of exposure of contacts to the index case in patients with MDR-TB.     

Recovery rate of NTM from AFB smear-positive sputum specimens at a medical centre in South Korea.

OBJECTIVE: To investigate the recovery rate of non-tuberculous mycobacteria (NTM) from acid-fast bacilli (AFB) smear-positive sputum specimens at a tertiary care medical centre in South Korea with a high pulmonary tuberculosis (PTB) burden. DESIGN: Retrospective analysis of data from AFB smear- and culture-positive sputum specimens collected between January 1998 and December 2001. RESULTS: Over 4 years, 1328 sputum specimens collected from 616 patients were AFB smear- and culture-positive. NTM were recovered from 9.1% (121/1328) of the smear-positive sputum specimens, and from 8.1% (50/616) of patients with smear-positive sputum. NTM were isolated at least twice in 94% (47/50) of the patients from whom NTM was recovered. The most common organism found was Mycobacterium avium complex, followed by M. abscessus. CONCLUSION: These results suggest that a substantial proportion of patients at a tertiary care medical centre in South Korea with AFB smear-positive sputum specimens may have NTM lung disease rather than PTB.     

Contact tracing using a new T-cell-based test: better correlation with tuberculosis exposure than the tuberculin skin test.

SETTING: Residential institution for alcoholics in Switzerland. OBJECTIVE: To compare the results of the tuberculin skin test (TST) and the new T-cell-based test for tuberculosis infection (T-SPOT.TB) in subjects exposed to a case of smear-positive pulmonary TB (PTB). DESIGN: After the notification of smear-positive PTB in a resident of an institution for alcoholics, contacts underwent TST and determination of Mycobacterium tuberculosis specific T-cells in blood by T-SPOT.TB. Results were analysed according to age, history of BCG vaccination, and level of exposure to the index case. RESULTS: There was no correlation between the level of exposure and the TST results, but the T-SPOT.TB results were significantly correlated with the level of exposure (P = 0.029, OR 5.00, 95%CI 1.05-23.86). Contacts who had been previously BCG-vaccinated were significantly more likely to have a positive TST than unvaccinated contacts (52% vs. 0%, P = 0.0003), but there was no influence of prior BCG vaccination on T-SPOT.TB results. CONCLUSIONS: T-SPOT.TB test results correlated better than TST with level of exposure to M. tuberculosis and were not confounded by prior BCG vaccination. This test allows better selection of contacts who should receive treatment for latent TB infection.     

Tuberculosis infection in children who are contacts of immigrant tuberculosis patients.

The present study aimed to determine what proportion of children who are in close contact with immigrant tuberculosis (TB) patients are infected with Mycobacterium tuberculosis. For 1.5 yrs, 14 municipal health services in The Netherlands collected data from all non-Dutch TB patients and their contacts. Close contacts aged < 16 yrs received a tuberculin skin test (TST). A positive TST was defined as an induration of > or = 10 mm among nonvaccinated children, and > or = 16 mm among bacille Calmette-Guérin-vaccinated children. In total, 244 patients had 359 close contacts aged < 16 yrs. Nine out of the 359 (2.5%) had TB. A TST test was given to 298 out of the 359 (83%). Of the 115 contacts of 44 extrapulmonary TB patients, three (3%) had a positive TST. Of the 186 contacts of 58 positive pulmonary TB patients, 30 (16%) had a positive TST. Contacts of sputum smear-positive patients significantly more often had a positive TST (25%), compared with the contacts of sputum smear-negative patients (7%). Children born abroad significantly more often had a positive TST (20%) than children born in The Netherlands (5%). In conclusion, the prevalence of active tuberculosis and latent tuberculosis infection among children who are close contacts of immigrant tuberculosis patients is high and warrants an expansion of contact investigation.     

Risk factors for tuberculosis infection among household contacts in Bangkok, Thailand

A cross-sectional study was conducted to determine the prevalence of tuberculosis infection and risk factors for tuberculosis infection among household contacts aged less than 15 years in Bangkok, Thailand, between August 2002 and September 2003. During the study period, 342 index cases with sputum smear positive pulmonary tuberculosis patients were recruited into the study and their 500 household contacts aged under 15 years were identified. The prevalence of tuberculosis infection among household contacts was found to be 47.80% (95%CI = 43.41-52.19). In multivariate analysis, a generalized estimating equation (GEE) was used to determine the risk factors for tuberculosis infection among household contacts. The results indicated that the risk of tuberculosis infection was significantly associated with close contact (adjusted OR = 3.31, 95%CI = 1.46-7.45), exposure to female index case (adjusted OR = 2.75, 95%CI = 1.25-6.08), exposure to mother with tuberculosis (adjusted OR = 3.82, 95%CI = 1.44-10.14), exposure to father with tuberculosis (adjusted OR = 2.55, 95%CI = 1.19-5.46), exposure to index case with cavitation on chest radiograph (adjusted OR = 4.43, 95%CI = 2.43-8.05), exposure to index case with 3+ sputum smear grade (adjusted OR = 3.85, 95%CI = 1.92-7.70), and living in crowded household (adjusted OR = 2.63, 95%CI = 1.18-5.85). The distribution of tuberculosis infection and risk factors among contact cases are significant for health care staff in strengthening and implementing tuberculosis control programs in Thailand.     

Association of prevalence of tuberculin reactions with closeness of contact among household contacts of new smear-positive pulmonary tuberculosis patients.

OBJECTIVES: Among household contacts of newly diagnosed smear-positive pulmonary tuberculosis (TB) patients, to examine the association of apparent tuberculosis transmission with the closeness and duration of contact. METHODS: Household contacts of newly diagnosed patients with smear-positive pulmonary TB were identified, as well as a healthy population sample. Household contacts were categorized into three groups based on closeness, regularity, and duration of contact with index cases. All subjects underwent tuberculin testing. RESULTS: Among the household contacts, 47 of 112 (42%) of very close/intimate contacts had positive tuberculin tests, compared to 121 of 356 (34%) close/ regular contacts and 23 of 178 (13%) not close/sporadic contacts and 55 of 355 (16%) of a healthy population sample. CONCLUSIONS: Even among household contacts of smear-positive pulmonary TB patients, there were major differences in the proximity and duration of contact which were strongly associated with differences in the prevalence of positive tuberculin reactions.     

BACTEC MGIT 960和BACT/ALERT 3D系统快速培养和鉴定痰中抗酸杆菌

目的对抗酸染色阳性痰行分枝杆菌培养和鉴定。方法采用萋一尼氏抗酸染色法对临床诊断肺结核患者的晨痰涂片直接镜检,抗酸染色阳性痰经BACTEC960和BACT/ALERT3D系统进行分枝杆菌培养,分别经对硝基苯甲酸（PNB）和噻吩-2-羧基肼（TCH）培养基生长试验行分枝杆菌菌群和结核分枝杆菌复合群菌种鉴定。结果抗酸染色阳性痰标本的分枝杆菌培养阳性率100％,大多数为结核分枝杆菌（9／10）,少数为非结核分枝杆菌（1／10）,最快6天即可报告分枝杆菌阳性培养。结论BACTEC 960和BACT／ALERT3D系统具有快速培养分枝杆菌作用,抗酸染色阳性痰有必要行分枝杆菌培养和鉴定,有利于肺结核与非结核分枝杆菌病的鉴别诊断、结核分枝杆菌菌种鉴定和抗结核药物敏感性试验。     

Is TB contact screening relevant in a developing country setting? Experiences from eastern Nepal, 1996-1998.

SETTING: A tuberculosis programme run by a non-governmental organisation in eight hill and mountain districts of eastern Nepal. OBJECTIVE: To assess the impact of contact screening on case-finding. DESIGN: A retrospective cohort study of contacts of smear-positive, smear-negative and extra-pulmonary tuberculosis patients diagnosed and registered during 1996-1998 ('index cases'). Contacts, defined as household members identified by index cases, were screened by sputum examination; two positive smears were taken to indicate smear-positive pulmonary disease. RESULTS: Approximately 50% (668) of registered cases identified contacts; 75% (2298) of the contacts identified provided one or more sputum specimens. An overall smear-positive case yield of 0.61% (14) was obtained from contacts tested, all except one of which were contacts of smear-positive index cases. For smear-positive index cases with a smear grading of > or = 2+, the yield was 7.2 times greater (P = 0.04) than for those with a grading of 1+. CONCLUSION: In this setting, sputum examination of household contacts of smear-negative and extrapulmonary tuberculosis cases is not justified. Further assessment is needed to evaluate the utility of testing contacts of smear-positive cases without symptom screening, and whether cost effectiveness can be improved by restricting testing to contacts of cases with high bacterial (> or = 2+) loads.     

A cluster of tuberculosis associated with use of a marijuana water pipe.

SETTING: New cases of pulmonary tuberculosis (TB) were noted in a cluster of young Caucasian males, an unusual ethnic group for this disease in Queensland, Australia. It was noted that marijuana water pipe ('bong') smoking was common amongst cases and contacts. OBJECTIVE: To report this cluster of TB and to investigate whether shared use of a marijuana water pipe was associated with transmission of TB. DESIGN: All contacts were identified and screened according to standard protocols. Cases were asked to list contacts with whom they had shared a marijuana water pipe. RESULTS: Five cases of open pulmonary TB were identified clinically and on sputum culture, and all isolates of Mycobacterium tuberculosis were identical on typing. Of 149 contacts identified, 114 (77%) completed screening, and 57 (50%) had significant tuberculin skin test (TST) reactions on follow-up. Of 45 contacts who had shared a marijuana water pipe with a case, 29 (64%) had a significant TST reaction. CONCLUSION: Sharing a marijuana water pipe with a case of pulmonary TB was associated with transmission of TB (OR 2.22, 95 % CI 0.96-5.17), although the most important risk factor for acquiring TB infection in this cluster was close household contact with a case (OR 4.91, 95% CI 1.13-20.70).