Negative Acid-fast Bacilli Smear Research Articles

Predictive Factors and Clinical Impacts of Delayed Isolation of Tuberculosis during Hospital Admission.

Delayed isolation of tuberculosis (TB) can cause unexpected exposure of healthcare workers (HCWs). This study identified the predictive factors and clinical impact of delayed isolation. We retrospectively reviewed the electronic medical records of index patients and HCWs who underwent contact investigation after TB exposure during hospitalization at the National Medical Center, between January 2018 and July 2021. Among the 25 index patients, 23 (92.0%) were diagnosed with TB based on the molecular assay, and 18 (72.0%) had a negative acid-fast bacilli smear. Sixteen (64.0%) patients were hospitalized via the emergency room, and 18 (72.0%) were admitted to a non-pulmonology/infectious disease department. According to the patterns of delayed isolation, patients were classified into five categories. Among 157 close-contact events in 125 HCWs, 75 (47.8%) occurred in Category A. Twenty-five (20%) HCWs had multiple TB exposures (n = 57 events), of whom 37 (64.9%) belonged to Category A (missed during emergency situations). After contact tracing, latent TB infection was diagnosed in one (1.2%) HCW in Category A, who was exposed during intubation. Delayed isolation and TB exposure mostly occurred during pre-admission in emergency situations. Effective TB screening and infection control are necessary to protect HCWs, especially those who routinely contact new patients in high-risk departments.

Surgical Intervention for Endobronchial Tuberculosis with Total Bronchial Occlusion: A Case Report

Introduction. Endobronchial Tuberculosis (EBTB) is a specific TB form affecting the tracheobronchial tree with microbial and histopathological evidence. Early diagnosis is essential to provide timely treatment and prevent complications but also proves difficult due to the low positive rate of acid–fast bacilli (AFB) staining of sputum smears and non–specific clinical and radiological findings. Case Illustration. We reported a 19–year–old man with a productive cough suspected of pulmonary tuberculosis, with a positive GeneXpert test and negative AFB smear. He received anti–tuberculosis drugs for six months. Although the symptoms initially seemed to improve, the patient complained of dyspnea during moderate activities in the sixth month. Chest x–ray showed complete atelectasis of the left lung. Further investigation with thorax computed tomography and confirmation with bronchoscopy revealed total occlusion of the left main bronchus. Left pneumonectomy was successfully conducted. Conclusion. Endobronchial tuberculosis may progress to an advanced stage despite adequate anti–tuberculosis drugs. Therefore, early diagnostic strategies are required to prevent the progression of the disease, particularly due to the insidious nature of its pathophysiological process

Abstract 16926: Outside The Box But All Squeezed In: A 23-year-old Man With Progressive Dyspnea After Overseas Travel

Case Presentation: A 23-year-old previously healthy man presented with progressive dyspnea. Physical examination revealed jugular venous distension and lower extremity edema. Laboratory testing demonstrated elevated B-type natriuretic peptide (193 pg/mL) and normal high sensitivity troponin. Echocardiogram revealed small pericardial effusion, respiratory variation in diastolic flow across the mitral valve, diastolic septal bounce, and annulus reversus ( Figure ). The differential diagnosis for constrictive pericarditis was broadly considered in the context of a recent febrile illness and frequent travel to Hawaii and Vietnam; we included infectious, autoimmune, and malignant etiologies. Cardiac magnetic resonance imaging revealed thickening and diffuse enhancement in the pericardium as well as ventricular interdependence. Chest CT identified hilar and anterior mediastinal lymphadenopathy. Laboratory testing was positive for QuantiFERON gold and negative for COVID-19, HIV, and ANA. Transbronchial biopsy demonstrated non-necrotizing granulomas with negative acid-fast bacilli smear, culture, and polymerase chain reaction for mycobacterial DNA. Re-examination identified a red-brown plaque on the patient’s thigh; biopsy showed granulomatous inflammation and rod-shaped organism with positive FITE staining. A presumed unifying diagnosis was made of extrapulmonary tuberculosis (TB) complicated by constrictive pericarditis. Discussion: Despite being a primarily pulmonary disease, systemic involvement can occur with TB with the heart being one of the most common extrapulmonary sites. This case highlights 1) the utility of extra-cardiac diagnostic testing (e.g., dermatologic biopsy) in the diagnosis of constrictive pericarditis, and 2) the diagnostic challenge associated with extrapulmonary TB, particularly paucibacillary disease that requires a detailed social history with “out-of-the-box” thinking.

Detection of <em>Mycobacterium leprae</em> using real-time PCR in paucibacillary leprosy patients with negative acid-fast bacilli smears

BACKGROUND Leprosy is an infectious disease that is still a health problem worldwide, including in Indonesia. The clinical symptoms are similar to other skin diseases and it is difficult to establish a diagnosis for paucibacillary (PB) leprosy. Current serological and histopathological tests have limitations, especially in patients with negative acid-fast bacilli (AFB). Serological tests often give false-negative results, while histopathological results often consist of non-specific inflammation. Probe-based real-time polymerase chain reaction (RT-PCR) assays is an alternative test that may be more sensitive and more specific to detect Mycobacterium leprae. METHODS This study was done in June 2015 until March 2016; detected M. leprae in PB patients with negative AFB smears using TaqMan® probe-based RT-PCR assay on slit skin scrapings and skin biopsy specimens from 24 patients. The skin scrapings were obtained from skin tissue on ear lobes, skin lesions, as well as those from biopsy. Samples were tested with RT-PCR while histopathological examinations were only performed on skin from biopsy. RESULTS The RT-PCR assay showed positive results of 21%, 25%, and 96% for specimens obtained from skin scrapings of the ear lobe, skin lesions, and skin biopsy, respectively. On the other hand, the positive rate for the histopathological test from skin biopsy was 79%. It indicated that the TaqMan® RT-PCR assay could increase the diagnostic capacity of histopathological examination by as much as 17%. CONCLUSIONS TaqMan® PCR assay can improve the diagnostic capacity of histopathological examinations, which could be used as the new gold standard for the diagnosis of leprosy.

MYCOBACTERIUM AVIUM COMPLEX MEDIASTINAL LYMPHADENITIS IN AN IMMUNOCOMPETENT ADOLESCENT WITH EROSION INTO THE AIRWAY

SESSION TITLE: Kid cases SESSION TYPE: Fellow Case Reports PRESENTED ON: 10/07/2018 03:30 PM - 04:30 PM INTRODUCTION: Mycobacterium avium complex (MAC) is associated with bronchiectasis and is seen in children with cervical lymphadenitis. It is rarely described in older immunocompetent children. CASE PRESENTATION: A 15-year-old male presented with 4 days of back pain, cough, fever, and pleuritic chest pain. Patient was febrile, 98% SpO2 on room air, tachycardic, with wheezing and rhonchi. D-dimer was elevated. Chest CT revealed a posterior mediastinal soft tissue mass (6.2 cm in diameter) with intra-lesional air abutting the right bronchus intermedius (Figure 1). MRI did not suggest a neurogenic tumor. Empiric IV antibiotics were initiated to treat a presumably infected bronchogenic duplication cyst. The mass was resected via VATS (Figure 2). Post-operatively, a persistent air leak developed. Due to concern for airway injury or bronchial fistula, flexible bronchoscopy was performed, revealing an atypical orifice along the medial wall of the bronchus intermedius (Figure 3). Interrogation revealed a sac like structure. This was presumed to be an accessory cardiac bronchus, a rare anatomic bronchial variant. This structure was in close proximity to the resected tissue and presumably communicated with the pleural space. Histologic evaluation of the resected soft tissue mass identified lymph nodes with necrotizing granulomas without airway or lung tissue. No pathogens were identified and acid-fast bacilli (AFB) smear was negative. A subsequent sputum specimen smear was AFB positive with positive identification of MAC via nucleic acid hybridization. Sputum culture grew MAC at 19 days. Immunologic and infectious evaluations were unremarkable. A treatment course of azithromycin, rifampin, and ethambutol was initiated. Repeat bronchoscopy with BAL performed 2 months after presentation revealed resolution of previous airway abnormality, with negative AFB smear and culture on BAL fluid. Chest CT obtained 3 months after antibiotic therapy revealed resolution of the posterior mediastinal mass. DISCUSSION: Initial bronchoscopy was suggestive of an underlying airway anomaly (cardiac bronchus) as a possible nidus for MAC infection, and subsequent mediastinal erosion. However, given lack of bronchoscopic and imaging evidence supporting a persistent airway anomaly, this case is most consistent with MAC associated mediastinal lymphadenitis complicated by formation of a bronchial fistula. CONCLUSIONS: This case highlights an unusual presentation of MAC mediastinal lymphadenitis with erosion into the airway in an immunocompetent teenager. Although rare in children, MAC mediastinal lymphadenitis needs to be considered in the differential diagnosis of mediastinal masses, especially in patients with respiratory symptoms. If there is evidence on chest imaging of close communication between a mediastinal mass and the airways, clinicians should have a low threshold to perform bronchoscopy to closely evaluate the airways. Reference #1: Nolt, D., Michaels, M. G., & Wald, E. R. (2003). Intrathoracic disease from nontuberculous mycobacteria in children: two cases and a review of the literature. Pediatrics, 112(5), e434-e434. Reference #2: Freeman, A. F., Olivier, K. N., Rubio, T. T., Bartlett, G., Ochi, J. W., Claypool, R. J., … & Holland, S. M. (2009). Intrathoracic nontuberculous mycobacterial infections in otherwise healthy children. Pediatric pulmonology, 44(11), 1051. Reference #3: Desir, A., & Ghaye, B. (2009). Congenital abnormalities of intrathoracic airways. Radiologic clinics of North America, 47(2), 203-225. DISCLOSURES: No relevant relationships by Jason Caboot, source=Web Response No relevant relationships by Benjamin Garren, source=Web Response

Evaluation of risk factors for false-negative results with an antigen-specific peripheral blood-based quantitative T cell assay (T-SPOT®. TB) in the diagnosis of active tuberculosis: A large-scale retrospective study in China.

ObjectiveTo investigate the diagnostic efficacy of an interferon-γ release assay, T-SPOT®.TB, for diagnosing active tuberculosis (TB) and to identify risk factors for false-negative results.MethodsThis retrospective study enrolled consecutive patients with active TB and with non-TB respiratory diseases to evaluate the risk factors for false-negative results when using the T-SPOT®.TB assay for the diagnosis of active TB. Patients with active TB were categorized as having confirmed pulmonary TB, clinically diagnosed pulmonary TB or extrapulmonary TB (EPTB).ResultsThis study analysed 4964 consecutive patients; 2425 with active TB and 2539 with non-TB respiratory diseases. Multivariate logistic regression analyses identified the following five factors that were all associated with an increased false-negative rate with the T-SPOT®.TB assay: increased age (odds ratio [OR] 1.018; 95% confidence interval [CI] 1.013, 1.024); decreased CD8+ count (OR 0.307; 95% CI 0.117, 0.803); negative sputum acid-fast bacilli (AFB) smear staining (OR 1.821; 95% CI 1.338, 2.477); negative mycobacterial cultures (OR 1.379; 95% CI 1.043, 1.824); and absence of EPTB (OR 1.291; 95% CI 1.026, 1.623).ConclusionsIncreased age, decreased CD8+ count, negative sputum AFB smear results, negative sputum mycobacterial cultures and absence of EPTB might lead to an increased false-negative rate when using the T-SPOT®.TB assay.

Pulmonary Langerhans Cell Histiocytosis Presenting With Unusual Radiologic Features

SESSION TITLE: Sarcoidosis and Cystic Lung Disease SESSION TYPE: Affiliate Case Report Poster PRESENTED ON: Tuesday, October 31, 2017 at 01:30 PM - 02:30 PM INTRODUCTION: Pulmonary Langerhans Cell Histiocytosis (PLCH) is a rare interstitial lung disease with characteristic features on computed tomography (CT) of nodular and cystic lesions in an upper to middle lung distribution. We present a case of PLCH with diffuse centrilobular ground glass nodularity and hemoptysis. CASE PRESENTATION: A 51 year-old Ukrainian female with a 10 pack-year smoking history presented with intermittent submassive hemoptysis over 6 months. Extensive environmental and occupational exposure history was unremarkable. Physical examination was notable for bibasilar crackles on auscultation. Vital signs showed normal saturation on room air. Laboratory data revealed Hemoglobin of 12 (Normal: 12-16), elevated c-reactive protein of 6.2 (Normal: 0-0.8), and positive Quantiferon Gold. Sputum returned with negative acid-fast bacilli smears, gram stains, and cultures. CT scan of the thorax revealed diffuse bilateral centrilobular ground glass nodularity without focal consolidation or mediastinal lymphadenopathy. Work-up for hypersensitivity pneumonitis and connective tissue diseases was negative. Video bronchoscopy with bronchoalveolar lavage yielded a predominance of alveolar macrophages (95%) with negative microbiology and cytology. Transbronchial biopsy revealed hemosiderin deposits and nonspecific inflammation. Unfortunately, she signed out against medical advice. One month later, she presented with worsening hemoptysis and repeat CT of the thorax demonstrated progression of diffuse bilateral centrilobular nodularity (fig. 1). Surgical lung biopsy was performed which revealed obliterative bronchiolitis with intraluminal blood, hemosiderin deposition, adjacent cyst formation, and nodules in various states of fibrosis and inflammation. Pathognomonic CD1-antigen stain was positive for peribronchial and intrabronchial Langerhans cells consistent with PLCH (fig. 2). Our patient’s hemoptysis and CT findings resolved with abstinence of smoking. DISCUSSION: Diffuse centrilobular nodules, as seen in our patient, have not yet been described in PLCH to the best of our knowledge. This radiologic pattern represents early changes with significant inflammatory infiltration as evidenced by biopsy. With advances in radiologic techniques and enhanced resolution new patterns may be identified. CONCLUSIONS: Further studies are needed to identify the spectrum of radiographic presentations, especially to determine if diffuse centrilobular nodular opacities represent earlier changes seen in PLCH. This will provide opportunities for early diagnosis with timely treatment and has potential prognostic implications. Reference #1: Juvet SC, Hwang D, Downey GP. Rare lung diseases III: Pulmonary Langerhans' cell histiocytosis. Candian Respiratory Journal: Journal of the Canadian Thoracic Society. 2010; 17(3):e55-62. DISCLOSURE: The following authors have nothing to disclose: Spencer Pugh, Anil Singh, Tina Dudney, Arseniy Tsapenko No Product/Research Disclosure Information

Delays in diagnosis and treatment of pulmonary tuberculosis in AFB smear-negative patients with pneumonia.

Diagnostic and treatment delays increase the severity and transmission of pulmonary tuberculosis (PTB). This study aimed to evaluate TB diagnostic and treatment delays in acid-fast bacilli (AFB) smear-negative patients. This was a retrospective observational study. Patients with positive AFB culture of Mycobacterium tuberculosis complex (MTC) were selected from among hospitalised patients with a diagnosis of pneumonia. Admission ward, anti-tuberculosis treatment and the duration of AFB culture were compared between smear-positive and smear-negative patients. Of the 70 patients with positive isolation of MTC in AFB culture, 27 (38.5%) were smear-negative; of these, 18 (66.7%) were not isolated while in hospital, and 17 (63%) were neither diagnosed nor treated for TB. In contrast, 41 of the 43 smear-positive patients (95.3%) were directly admitted or quickly transferred to the isolation room and started on anti-tuberculosis treatment (P < 0.001). Samples from smear-negative patients required more time to grow MTC in AFB culture than those of smear-positive patients (23 days vs. 14 days, P < 0.001). Diabetes was significantly associated with AFB smear positivity, with an odds ratio of 12.2. Negative AFB smears caused significant diagnostic and treatment delay. Patients staying in the general ward were exposed to TB patients who were not diagnosed in time.

Pulmonary Mycobacterium bovis Infection: Uncommon Modes of Transmission

SESSION TITLE: Student/Resident Case Report Poster - Chest Infections II SESSION TYPE: Student/Resident Case Report Poster PRESENTED ON: Tuesday, October 25, 2016 at 01:30 PM - 02:30 PM INTRODUCTION: Tumor necrosis factor (TNF) blockers are being used increasingly in the management of inflammatory bowel disease, especially Crohn’s disease. We present a case of pulmonary Mycobacterium bovis infection in a patient treated with Adalimumab, and subsequently with Infliximab. CASE PRESENTATION: A 19 year old woman with a history of Crohn’s disease was admitted because of fevers and dry cough for 3 days. She had fever of 103°C with generalized weakness, chills and sweating. She had been started on Infliximab 2 weeks prior to the presentation. Her other medications included azathioprine and 6 mercaptopurine. She had been previously treated with Adalimumab. She had recently travelled to Los Angeles, but denied consuming any unpasteurized milk products. She denied any animal contact in the recent past.. She was found to have bibasal lung nodules on a prior abdominal CT scan. Chest CT revelaed extensive small bilateral nodules, and scattered tree- in-bud appearance, raising the concern of mycobacterial disease. In view of negative acid-fast bacilli smears of sputum and a positive interferon gamma release assay, pulmonary wedge biopsy was obtained which revealed granulomata with caseous necrosis and acid-fast bacilli. Organisms were subsequently speciated as Mycobacterium bovis. Her treatment was complicated by Isoniazid induced elevation of liver function tests and pancreatitis, eventually requiring a modification in the treatment regimen to include Moxifloxacin, Ethambutol and Rifampin. The patient was discharged home with appointments for pulmonary, infectious disease and gastroenterology follow up. DISCUSSION: Mycobacterium bovis infection may be acquired through different modes of transmission, the most common being animal to human via consumption of unpasteurized milk or milk products (1). However human to human transmission has been reported, which is influenced by host and environmental factors (2). Adalimumab and infliximab induced suppression of phagosome maturation plays a factor in the pathogenesis of M. bovis infection. (3) CONCLUSIONS: TNF blockers can increase the risk of Mycobacterium bovis infection acquired secondary to other uncommon modes of transmission such as aerosolized animal to human and human to human transmission in susceptible host. Reference #1: Centers for Disease Control and Prevention (CDC. “Human tuberculosis caused by Mycobacterium bovis--New York City, 2001-2004.” MMWR. Morbidity and mortality weekly report 54.24 (2005): 605. Reference #2: Evans, Jason T., et al. “Cluster of human tuberculosis caused by Mycobacterium bovis: evidence for person-to-person transmission in the UK.”The Lancet 369.9569 (2007): 1270-1276. Reference #3: Harris, James, Jayne C. Hope, and Joseph Keane. “Tumor necrosis factor blockers influence macrophage responses to Mycobacterium tuberculosis.”Journal of Infectious Diseases 198.12 (2008): 1842-1850. DISCLOSURE: The following authors have nothing to disclose: Mangalore Amith Shenoy, Selma Demir, Pavan Gorukanti, Pavan Irukulla, Amit Agarwal, Prarthna Chandar, Ishan Malhotra, Kabu Chawla, William Pascal No Product/Research Disclosure Information

A retrospective review of a tertiary Hospital's isolation and de-isolation policy for suspected pulmonary tuberculosis.

BackgroundEffective protocols for the isolation and de-isolation of patients with suspected pulmonary tuberculosis (PTB) are essential determinants of health-care costs. Early de-isolation needs to be balanced with the need to prevent nosocomial transmission of PTB. The aim of our study was to evaluate the efficiency of our hospital’s current protocol for isolating and de-isolating patients with suspected PTB, in particular assessing the timeliness to de-isolation of patients with AFB smear negative respiratory samples.MethodsWe retrospectively reviewed 121 patients with suspected PTB who were admitted to our hospital’s isolation ward. We analyzed the time spent in isolation, the total number of respiratory samples that were collected for each patient and the time taken from collection of the first respiratory sample to release of the result of third respiratory sample for acid-fast bacilli (AFB) smear. We also calculated the direct cost of isolation for each patient.ResultsThe mean and median number of AFB smears for each patient was three. Thirty percent of patients had four or more AFB smears taken and 20% were de-isolated before the results of three negative AFB smears were obtained. The mean duration of isolation was significantly shorter in patients who had fewer than three negative AFB smears compared to those who had three or more negative AFB smears (three days vs. five days, p <0.01). The mean cost in patients who were de-isolated before three negative smears were obtained was USD 947 compared to USD 1,636 in those were only de-isolated after three negative AFB smears (p <0.01).ConclusionsOur study suggests that our institution’s current infection control policy for the isolation of patients with suspected PTB is fairly satisfactory, but may need to be tightened further to prevent true cases of PTB being de-isolated prematurely. However, there may be instances when patients could potentially be de-isolated more quickly without risk to others, thus saving on the use of limited resources and costs to patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-014-0547-7) contains supplementary material, which is available to authorized users.

Culture conversion rate at 2 months of treatment according to diagnostic methods among patients with culture-positive pulmonary tuberculosis.

IntroductionThe culture-negative conversion rate of sputum after 2 months of treatment in patients with pulmonary tuberculosis (TB) is used as a reliable surrogate marker for relapse after completion of treatment. We hypothesized that culture conversion of sputum at 2 months of anti-TB treatment and the time to culture conversion are different among pulmonary TB patients who are diagnosed using different methods.MethodsCulture-confirmed pulmonary TB patients who were diagnosed between 1 January, 2011 and 31 December, 2012 were classified into three groups based on the diagnostic method that prompted treatment initiation: positive acid-fast bacilli (AFB) staining of sputum (smear-positive group), negative AFB staining, but Mycobacterium tuberculosis was cultured from sputum (culture-positive group), and positive AFB staining, positive polymerase chain reaction (PCR) for M. tuberculosis, or culture of M. tuberculosis from a bronchoscopic specimen (bronchoscopy group). Rates of negative mycobacterial culture conversion at 2 months of anti-TB treatment and the time to negative culture conversion of sputum were compared among the three groups.ResultsA total of 203 patients with culture-confirmed pulmonary TB were included in the final analysis. TB patients in the culture-positive group (94.1%) and the bronchoscopy group (97.6%) showed a higher culture conversion rate at 2 months of treatment than those in the smear-positive group (78.7%, P = 0.001). Additionally, the time to culture conversion was longer in the smear-positive group (median, 40 days) than in the culture-positive (median, 19 days; P = 0.009) and bronchoscopy groups (median, 29 days; P = 0.004).ConclusionsThe higher culture conversion rate at 2 months and the shorter time to culture conversion among pulmonary TB patients with a negative AFB smear suggests the feasibility of shortening treatment duration and isolation in these patients.

Diagnostic accuracy of Xpert® MTB/RIF on bronchoscopy specimens in patients with suspected pulmonary tuberculosis

To determine the diagnostic accuracy of the Xpert® MTB/RIF assay using samples obtained through bronchoscopy in patients with suspected pulmonary tuberculosis (PTB). We retrospectively reviewed the records of patients with suspected PTB for whom the Xpert MTB/RIF assay was performed on bronchoscopy specimens. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for the diagnosis of active PTB were calculated for acid-fast bacilli (AFB) smear microscopy and the Xpert assay using culture of Mycobacterium tuberculosis from sputum or bronchoscopy specimens as a reference standard. A total of 132 patients were included in the final analysis. Of these, 38 had culture-confirmed PTB. The sensitivity of the Xpert assay using bronchial washing or bronchoalveolar lavage (BAL) fluid for the diagnosis of PTB was 81.6%, and specificity was 100%. The PPV and NPV were 100% and 92.1%, respectively. The sensitivity and specificity of AFB smear microscopy were respectively 13.2% and 98.8%. The Xpert assay on bronchoscopy specimens provided an accurate diagnosis of PTB in patients who had a negative AFB smear or who could not produce sputum.

Diagnostic value of FASH ultrasound and chest X-ray in HIV-co-infected patients with abdominal tuberculosis [Notes from the field

In human immunodeficiency virus (HIV) co-infected tuberculosis (TB) patients with negative acid-fast bacilli smears, chest radiography (CXR) is usually the first imaging step in the diagnostic work-up. Ultrasound, also in the form of focused assessment with sonography for TB-HIV (FASH), is an additional imaging modality used to diagnose extra-pulmonary TB (EPTB). Findings from 82 patients with abdominal TB diagnosed by ultrasound were analysed and compared with CXR results. Enlarged abdominal lymph nodes were seen in 75.6% of the patients, spleen abscesses in 41.2% and liver lesions in 30.6%. CXR showed a miliary pattern in 21.9% of the patients; 26.8% of the CXR had no radiological changes suggestive of pulmonary TB. This patient group would benefit from ultrasound in diagnostic algorithms for HIV-associated EPTB.

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

BackgroundThis 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.MethodsWe 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.ResultsOf 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%.ConclusionsFOB 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.

Impact of smear microscopy results and observed therapy on tuberculosis treatment in Mombasa, Kenya

Tuberculosis (TB) treatment center at Coast Provincial General Hospital in Mombasa, Kenya. To describe TB management practices in a facility in coastal Kenya and identify factors associated with poor treatment outcomes. Retrospective review of patient treatment records from January 2008 to June 2009. Treatment outcomes of patients were classified as treatment success (cure or treatment completion) or poor treatment outcome (treatment failure, death or default). Relative risk regression was used to determine the association between exposures of interest and poor treatment outcomes. Records were obtained from a total of 183 patients: 142 (78%) had pulmonary TB, 68 (37%) were human immunodeficiency virus (HIV) infected and 81 (44%) had acid-fast bacilli (AFB) positive smear micros- copy. Most treated individuals (86%) achieved a successful treatment outcome as defined by the World Health Organization. Of those with poor treatment outcomes, 64% defaulted, 32% died, and 4% failed treatment. Initial negative AFB smear and HIV co-infection were associated with poor treatment outcomes (RR 3.32, 95%CI 1.22-8.99 and RR 4.61, 95%CI 1.69- 12.59, respectively). Strategies to accelerate accurate diagnosis of smear-negative TB and increase patient retention during treatment, especially in HIV co-infected individuals, are needed to reduce poor treatment outcomes in Kenya.

Chronic Skin Lesions in a Construction Worker

Diagnosis: multibacillary cutaneous tuberculosis. Examination of shave biopsy samples obtained from the le sions revealed multiple granulomas and acid-fast bacilli (Figures 1 and 2). Nucleic acid amplification testing (Gen-Probe) of the shave biopsy specimens had results that were positive for My cobacterium tuberculosis complex (MTB), and cultures from the biopsy site were positive for the same organism. Three sputum samples were obtained for fluorochrome stain, despite normal chest radiograph and computed tomography findings. Al though sputum samples had negative acid-fast bacilli smear results, MTB was isolated after cultures were incubated for 2 weeks. The patient was treated with rifampin, isoniazid, pyr azinamide, and ethambutol. Cutaneous tuberculosis is an uncommon presentation of tu

Diagnostic value of endobronchial ultrasonography for pulmonary tuberculosis

We sought to compare the diagnostic yields of acid-fast bacilli smears and Mycobacterium tuberculosis cultures in terms of bronchoalveolar lavage fluid and histologic examination of transbronchial lung biopsy specimens for pulmonary tuberculosis by using bronchoscopy with versus without endobronchial ultrasonography in patients with negative acid-fast bacilli smears or no sputum production. From June 2005 to July 2006, a total of 451 patients were given diagnoses of and treated for pulmonary tuberculosis in a university-affiliated hospital. Among them, 121 patients who received bronchoscopy because of sputum-negative conditions were recruited. Of these, 73 patients received bronchoscopy with endobronchial ultrasonography, and 48 patients received conventional bronchoscopy. Patients who received bronchoscopy with endobronchial ultrasonography had higher diagnostic yields of acid-fast bacilli smears (31.5% vs 12.5%, P = .018) in bronchoalveolar lavage fluid, M tuberculosis in bronchoalveolar lavage fluid (67.1% vs 47.9%, P = .024), and pathologic reports of tuberculosis in transbronchial lung biopsy specimens (32.9% vs 4.2%, P < .0001) than patients who received conventional bronchoscopy. With the aid of endobronchial ultrasonography, the overall diagnostic yield for tuberculosis by using bronchoscopic procedures (smears and cultures of bronchoalveolar lavage fluid and transbronchial lung biopsy specimens) was higher (80.8%) than for those who did not undergo endobronchial ultrasonography (58.3%, P = .035). The addition of endobronchial ultrasonography to diagnostic bronchoscopy increased the sensitivity for proving the presence of tuberculosis in a population of patients with negative acid-fast bacilli smears or no sputum production.

Buruli Ulcer in Long-Term Traveler to Senegal

To the Editor: Buruli ulcer (BU) is caused by infection of subcutaneous fat with the environmental pathogen Mycobacterium ulcerans. BU has been reported or suspected in more than 30 countries. It has never been reported in Senegal and Guinea-Bissau (1). We report a case of travel-associated BU in a French traveler to Senegal. The patient was a 24-year-old Caucasian man who came to the University Hospital of Bordeaux, France, with a nonhealing lesion on the anterior left leg that had been present for ≈12 weeks. The patient had traveled in Senegal to the border of Guinea-Bissau from September 2006 through August 2007. His trip had begun in Dakar and proceeded south to the districts of Kaolack, Toubacouta, and Casamance. The patient stayed in Casamance during the rainy season from June 2007 through August 2007. He had been working on construction of wood dugouts, had been bare-legged regularly, and had been in contact with stagnant water. He first noticed a lesion during June 2007, which had gradually increased to a small, centrally crusted ulcer. By the end of August 2007 (week 8 of the lesion), skin examination showed a 3 × 6-cm necrotizing ulcer with central crusting and an erythematous border (Figure). The lesion was not warm or tender but generated a seropurulent discharge. Concurrently, palpable left inguinal lymph nodes were observed. Figure Ulcer (3 × 6 cm) on anterior side of the left leg of the patient, showing an erythematous border. Bacteriologic swabs identified Staphylococcus aureus and group A Streptoccocus pyogenes. Two punch-biopsy specimens were taken from the border of the lesion. Histologic analysis showed nonspecific acute and chronic dermal inflammation with necrotizing granulomas that extended into the subcutaneous tissues, suggestive of infection with atypical Mycobacterium spp. Bacteriologic examination did not identify acid-fast bacilli (negative direct smear result after Ziehl-Neelsen staining) or other specific microorganisms (negative direct smear results after periodic acid–Schiff, Giemsa, and Gram staining). Tissue specimens were placed into BACTEC 12B broth (Becton Dickinson, Franklin Lakes, NJ, USA) (incubated at 35°C) and onto Lowenstein-Jensen slants (incubated at 30°C). No growth was detected after 42 days. On the basis of clinical findings, we suspected a diagnosis of BU. Taq-Man real-time quantitative PCR that used primers for 2 M. ulcerans–specific genes (insertion sequence 2404 and ketoreductase B gene) (2,3) and negative controls showed positive results for DNA from both biopsy specimens. A normalized standard curve was constructed, which indicated a bacterial load of ≈6 × 103 organisms/g of tissue. Laboratory investigations indicated a total leukocyte count of 16,400 cells/μL (reference range 3,600–10,000 cells/μL) and a C-reactive protein level of 0.59 mg/mL (reference value <0.01 mg/mL). Results of radiologic investigations were normal. The patient was treated with rifampin (600 mg/day) and moxifloxacin (400 mg/day) for 12 weeks. Additional surgical excision was planned 4 weeks after treatment was begun. Unfortunately, 15 days later, the patient was lost to follow-up. BU has been reported in many West African countries, with Guinea being the northern limit of reported cases. Detection of this case of BU suggests that the region in West Africa endemic for this disease has been underestimated or is expanding. Infection in the traveler may have occurred in Casamance, if one assumes an incubation period of 6 weeks to 3 months. Further cases should be actively sought in this region and adjoining districts visited to evaluate the geographic extent of the disease. The environmental reservoir and mode of transmission of BU in our patient are unknown. Exposure of unprotected skin with stagnant or slow-flowing water is linked with BU. Our patient reported prolonged contact with water during his occupation. Recent studies implicating aquatic predator insects (4,5) and mosquitoes (6) in transmission of BU suggest that use of insect repellents and protective clothing may help prevent infection. The diagnosis of BU in this patient relied on the PCR detection of 2 M. ulcerans–specific genes; this procedure is considered adequate (7,8). The relatively low number of organisms detected may explain the negative acid-fast bacilli smear and culture results (9). Our report of M. ulcerans infection from Senegal is not surprising because southern Senegal shares similar ecologic features with neighboring affected countries, especially during the heavy rainy season. Although BU is a disease that affects mainly persons in recognized disease-endemic areas, this case emphasizes that tropical skin ulcers should be considered in differential diagnosis of BU in travelers returning from disease-endemic countries (1,10). Diagnostic delays can be avoided by use of M. ulcerans–specific PCR, a test available from World Health Organization collaborating laboratories, which enables rapid confirmation of diagnosis of BU.

Rapid Diagnosis of Smear-negative Tuberculosis by Bronchoalveolar Lavage Enzyme-linked Immunospot

Rationale: In a large proportion of patients with active pulmonary tuberculosis (pTB), acid-fast bacilli smear results for sputum and bronchial secretions are negative. Detectable growth of Mycobacterium tuberculosis (MTB) in cultures takes several weeks and MTB-specific DNA amplification results on sputum and bronchial secretions are variable in these patients.Objective: We investigated whether a rapid diagnosis of pTB can be established by enumeration of MTB-specific mononuclear cells from bronchoalveolar lavage (BAL) fluid in routine clinical practice.Methods: Patients presenting to a tertiary hospital with medical histories and pulmonary infiltrates compatible with tuberculosis, and negative acid-fast bacilli smear results (three) from sputum, were prospectively enrolled in this study. An MTB-specific enzyme-linked immunospot assay (ELISPOT [T-SPOT.TB; Oxford Immunotec, Abingdon, UK]) with early antigenic target-6 (ESAT-6) and culture filtrate protein-10 (CFP-10) peptides was performed on peripheral b...

Adult cystic fibrosis presenting with recurrent non-tuberculous mycobacterial infections

In November, 1997, a previously healthy 54-year-old white man presented with productive cough, low-grade fever, and chills resistant to outpatient treatment with clarithromycin and cefpodoxime proxetil. CT of the chest showed consolidation of the left lower lobe and lingula. Spirometry was normal, and HIV serology was negative. Sputum showed acid-fast bacilli (AFB) and cultures grew Mycobacterium avium intracellulare. The patient was treated with rifampicin, ethambutol hydrochloride, and clarithromycin for 2 years. In January, 2002, he presented to our clinic with recurrent symptoms. Chest CT showed only linear densities in the left lower lobe. AFB smears were again positive. Cultures grew Mycobacterium chelonae and the patient was treated with doxycycline, clarithromycin, and ciprofl oxacin. Several months later a repeat AFB smear was positive, with cultures growing Mycobacterium abcessus and M avium intracellulare. He was admitted to our unit, and highresolution chest CT showed mild bilateral central bronchiectasis. Barium swallow showed a normal swallowing mechanism without gastro-oesophageal refl ux and no laryngeal penetration. Tests for antinuclear antibody and rheumatoid factor were negative. α-1 antitrypsin and immuno globulin concentrations were normal. He was discharged 10 days after admission. Despite repeated attempts, the patient had fathered no children, therefore a sweat chloride test was done as an outpatient; the concentration was high at 96 mmol/L (normal 40–60 mmol/L). Cystic fi brosis (CF) genotyping showed that the patient was heterozygous for two diff erent CF trans membrane conductance regulator gene alleles: δF508 and R117C. The patient was treated with ciprofl axacin, clarithromycin, and ethambutol for 3 years. When last seen in March, 2006, the patient had negligible sputum production, and AFB smears have been negative since 2004. Non-tuberculous mycobacteria (NTM) are free-living organisms that are ubiquitous in the environment. Occasional isolates of NTM were generally thought to be contaminants or colonisers until the second half of the 20th century. As the prevalence of Mycobacterium tuberculosis declined in developed nations and modern microbiological methods were developed, the importance of NTM in human disease became increasingly evident. By the early 1990s, laboratories in the USA informally reported that about two-thirds of recovered mycobacteria species were NTM. Some of this increase is related to the high rate of disseminated M avium complex disease in patients with AIDS; however, there could also have been an increase in the rate of NTM infections in other groups of patients, such as those with CF. The classic description of NTM pulmonary infection is that of a patient with cavitary infi ltrates and underlying lung disease. We have seen two patients in their mid-50s, who developed recurrent NTM pulmonary infections and were sub sequently diagnosed with CF. Our second patient had congenital absence of the vas deferens and normal sweat chloride concentration; he was confi rmed to have CF by genotyping showing the δ508 and D1152H alleles. Among adults with CF, 63% are aged 18–29 years, 25% 30–39 years, 10% 40–49 years, and 2% over 50 years ; adults will represent >40% of the US cystic fi brosis population in 2005. Among the 22 301 patients in the 2000 CF Foundation registry, the diagnosis was established after the age of 17 years in only 831 (3·7%); sweat chloride tests were abnormal in 90% of cases. Although NTM infections in CF are well described, recurrent NTM infection as the initial presentation of CF has not been described. The reported prevalence of NTM in CF ranges from 3% to 30%. Contamination of mycobacterial cultures (especially by Pseudomonas aeruginosa) can lead to underestimation of the prevalence of NTM infection in CF. Controversy surrounds the distinction between NTM infection and simple colonisation in CF. Symptomatic patients with persistently positive AFB smears and new radiographic abnormalities are most likely to be truly infected. Patients with negative AFB smears but positive cultures with low numbers of colonyforming units are probably colonised. We believe our patients were actively infected and not just colonised because they were symptomatic and had repeatedly positive AFB smears, high colony-forming unit counts on culture, and new radiographic changes. Both also improved with appropriate anti-NTM therapy. Our patients were pancreatic suffi cient and their respiratory symptoms were mild and delayed in comparison to more severe CF phenotypes. They remain free of sputum colonisation by pseudomonas at age 60 years (case history presented in detail) and 57 years. We postulate that the benign course of their illness is related to the fact that they are heterozygous for two diff erent CF gene alleles, the usual δF508 and R117C/ D1152H—the latter two are associated with milder disease. We conclude that in patients with recurrent NTM infections and new radiographic abnormalities, a diagnosis of CF should be considered irrespective of the patient’s age.