Negative Sputum Smear Research Articles

Impact of CD4 Count on sputum smear for AFB in HIV-TB Co infection

Background: Human immunodeficiency virus (HIV) infection is a major threat in the world population and in the control of tuberculosis in developing countries. HIV-TB co infected patients with CD4 counts above 200 cells/cu µl, are likely to have typical symptoms and most of the sputum shows positive for acid fast bacilli (AFB). Patient withCD4 count less than 200 are with high risk of getting (Tuberculosis) TB, but diagnosis is difficult as there is more chances of sputum becoming negative, which requires sputum culture for diagnosis of (TB). Although sputum smear negativity is high in most cases of dual infection, particularly in patients with low immunity, it is an essential component in the diagnosis of tuberculosis in countries like India. Methodology: A cross sectional study of 50 HIV-TB patients admitted to tertiary care hospital were studied for correlation between CD4 count and sputum smear results. Results: 50 HIV-TB patients studied for a period of 1 year. Majority were in the age group of 30-40 years 20 (78%). In the study 29 (58%) were males and 21(42%) were females. The common presentations were cough 48 (96%), fever 44 (88%), weight loss 42(84%) and diarrhoea 25(50%). Mean CD4 count being 146.6±88. Most patients had CD4 count < 200 cells/cu µl. Mean CD4 count in sputum positive TB was 254.8±77.3 and in sputum negative TB was 97.2±33.8. Conclusion: Patients with CD4 count > 200cells/cuµl are likely to have sputum positive pulmonary TB and typical presentations. Patients with CD4count < 200cells/cuµl are more of sputum negative pulmonary TB with atypical presentations which poses diagnostic difficulty and needs newer diagnostic tests. Key words: HIV-TB co infected patients, CD4 count, Sputum for AFB

Diagnostic value of nine nucleic acid amplification test systems for Mycobacterium tuberculosis complex

Objective: In this study, nine commercial Nucleic Acid Amplification Test Systems (NAATs) were evaluated for diagnostic performance of Mycobacterium tuberculosis complex (MTBC) from smear positive sputum species (SPss) and smear negative sputum specimens (SNss). Methods: Sixty SPss and 55 SNss were examined microscopically by Ehrlich Ziehl Neelsen (EZN) staining method, and also inoculated on Lowenstein Jensen (LJ) medium for culture. The sensitivity and specificity of nine NAATs were calculated according to LJ culture method accepted as gold standard. Results: When LJ culture results were taken as gold standard; the sensitivity rates of method COBAS Amplicor MTB (Method A), GenProbe MTD (Method B), Cobas TaqMan MTB PCR (Method C), iCycler iQ RT PCR (Method D), TaqMan PCR AB 5700 (Method E), TaqMan PCR AB7700 (Method F), LightCycler® 480 RT PCR (Method G), Rotor Gene RT PCR (Method H) and the AdvanSure TB/NTM RT PCR (Method I) for SPss were 98.3 %, 93.3 %, 96.7 %, 100 %, 93.3 %, 100 %, 100 %, 100 % and 100 %, respectively. The sensitivity was 53.84% for the methods A, B, D, E, G and I; 38.46% for the method C and H; 61.5% for the method F for the method I in SNss. There were no statistical significant differences between the nine NAATs (p≥0.05). The specificity was 100% for all nine NAATs in SNss. The positivity rates of methods were 53.8% for methods A, B, D, E, G, I; 38.5% for methods C and H, and 61.5% for method F in SNss. These rates were 100% for D, F, G, H and I; 98.3% for method A; 96.7% for method C; 93,3% for methods B and E in SPss. Statistical analysis showed that there was no statistically significant differences among the nine NAATs (p≥0.05). Conclusion: It is concluded that the nine NAATs might be useful for detecting MTBC from SPss, but not effective for SNss. J Microbiol Infect Dis 2015;5(3): 103-109 Key words: Tuberculosis, polymerase chain reaction, nucleic acid amplification test, smear positive, smear negative, sputum

Bilateral Upper Zone Patchy Opacities on the Chest Radiography Taken for Screening in a Patient without Any Smptoms: What Is Your Diagnosis?

A 20-year-old male patient who worked as a salesman was referred to the Department of Chest Diseases due to opacities seen in the upper zones of both lungs on the posteroanterior chest radiography taken for screening in the tuberculosis control dispensary. The patient had no complaint, and the physical examination revealed no pathological finding. His arterial blood pressure was 110/70 mmHg, pulse was 88/min, temperature was 36.7°C, and SpO2 was 97% (oxygen-free). The results of laboratory analyses were found to be as follows: white blood cell count, 8.07×103/μL; eosinophils, 3.46%; hemoglobin, 16.6 g/dL; hematocrit, 47.8%; platelet count, 274,000/μL; complete urine test, normal; sedimentation, 2 mm/hour; C-reactive protein, 1.06 mg/dL; aspartate aminotransferase, 51 U/L; alanine aminotransferase, 78 U/L; and urea, 25 mg/dL. In arterial blood gas, the value of PO2 was 93.7 mmHg, PCO2 was 33.7 mmHg, HCO3 was 21.1 mmoL/L, SaO2 was 97.9%, and pH was 7.38. The patient’s posteroanterior chest radiography revealed diffuse patchy opacities in the upper and middle zones of both lungs (Figure 1). The patient had three negative sputum smear reports for acid-fast bacillus (AFB). There was a restrictive type disorder on the spirometry of the patient, and carbon monoxide diffusing capacity (DLCO) and DLCO/VA was measured as 64% and 98% respectively. High-resolution computed tomography (HRCT) of the chest revealed patchy ground-glass areas with peripheral localization,

Factors associated with time to mandatory tuberculosis notification in the Somme department, France

BackgroundThe associated factors contributing to a delay in mandatory tuberculosis notification in the Somme department, France, are not yet known. The objective of this study was to analyze these factors. MethodsAll reported cases of tuberculosis between 2007 and 2011 were retrospectively included. Univariate and multivariate analyses were conducted to investigate the factors associated with a short time to notification, i.e., ≤48h. ResultsBetween 2007 and 2011, a total of 175 cases of tuberculosis were reported to the Somme Regional Health Agency. Of the 145 (83.8%) cases of tuberculosis with at least one pulmonary location, 57.7% had a positive sputum smear. The mean time between the diagnosis of tuberculosis and mandatory notification was 6.1 days. It was 2.6 days for tuberculosis cases with a positive sputum smear versus 8.3 days for cases with a negative sputum smear; 2.0 days for severe cases and 6.3 days for simpler forms. In multivariate analysis, only a positive sputum smear was significantly associated with a short time to mandatory notification (OR 2.44; 95%CI 1.18–5.00; P=0.02). ConclusionThe time to mandatory notification is longer than recommended. Better collaboration between the parties involved in tuberculosis control and their continuing medical education could reduce this delay in the Somme department.

Identifikasi Bakteri Tahan Asam (BTA) pada Pasien Suspek Tuberculosis di Puskesmas Ngronggot, Kabupaten Nganjuk, Jawa Timur

Tuberculosis (TB) is an infectious disease caused byMycobacterium tuberculosis that can invade the lungs as a primary infection which is a major health problem in developing countries. The purpose of this study to identification Acid Resistant Bacteria in patients with symptoms of tuberculosis in the region Ngronggot health center, district Nganjuk.&#x0D; This type of study was a descriptive study. The sample in this study is the sputum of patients with suspected tuberculosis. The study was conducted in district health centers Nganjuk Ngronggot on May 14 to June 30, 2012 were 116 patients with symptoms of cough for more than three weeks and gained 7.76% or 9 people who suffer from tuberculosis with positive sputum smear examination. And the obtained results of 92.24% or 107 people with negative sputum smear examination.

Trends in Tuberculosis Cases Among Nursing Home Residents, California, 2000 to 2009.

To examine trends in tuberculosis (TB) incidence and to compare demographic and clinical characteristics of nursing home (NH) residents and community-dwelling older adults. Prospective TB surveillance. TB cases reported in California from 2000 to 2009. TB patients aged 65 and older. Trends in TB incidence per 100,000 population were assessed using Poisson regression. Demographic and clinical characteristics were compared using the chi-square or Wilcoxon rank-sum test. Among NH residents, risk factors for death during TB treatment were identified using logistic regression. From 2000 to 2009, TB incidence rates decreased significantly, from 15.9/100,000 to 8.4/100,000 (-44%, 95% confidence interval (CI)=-66% to -7%) for NH residents and from 21.2/100,000 to 15.0/100,000 (-27%, 95% CI=-29% to -24%) for community-dwelling older adults. Overall, 211 TB cases among NH residents and 6,518 cases among community-dwelling older adults were reported. NH residents were more likely than community-dwelling older adults to be older (median age 81 vs 75, P<.001), have a negative acid-fast bacilli sputum smear and positive culture (37% vs 28%, P<.001), and die while undergoing TB treatment (44% vs 14%, P<.001), and were less likely to have a positive tuberculin skin test (TST) (28% vs 44%, P<.001) and have TB care provided by a health department (20% vs 59%, P<.001). In multivariable analysis, NH residents who had a positive TST were less likely to die while undergoing TB treatment (odds ratio=0.39, 95% CI=0.16-0.96). TB incidence rates were lower, and reductions in incidence were greater among NH residents; community-dwelling older adults had higher TB rates and smaller reductions in incidence. Interventions that promote timely detection and treatment of TB infection and disease may be needed to reduce morbidity and mortality among NH residents.

A Novel Reporter Phage To Detect Tuberculosis and Rifampin Resistance in a High-HIV-Burden Population.

Improved diagnostics and drug susceptibility testing for Mycobacterium tuberculosis are urgently needed. We developed a more powerful mycobacteriophage (Φ(2)GFP10) with a fluorescent reporter. Fluorescence-activated cell sorting (FACS) allows for rapid enumeration of metabolically active bacilli after phage infection. We compared the reporter phage assay to GeneXpert MTB/RIF for detection of M. tuberculosis and rifampin (RIF) resistance in sputum. Patients suspected to have tuberculosis were prospectively enrolled in Durban, South Africa. Sputum was incubated with Φ(2)GFP10, in the presence and absence of RIF, and bacilli were enumerated using FACS. Sensitivity and specificity were compared to those of GeneXpert MTB/RIF with an M. tuberculosis culture as the reference standard. A total of 158 patients were prospectively enrolled. Overall sensitivity for M. tuberculosis was 95.90% (95% confidence interval (CI), 90.69% to 98.64%), and specificity was 83.33% (95% CI, 67.18% to 93.59%). In acid-fast bacillus (AFB)-negative sputum, sensitivity was 88.89% (95% CI, 73.92% to 96.82%), and specificity was 83.33% (95% CI, 67.18% to 93.59%). Sensitivity for RIF-resistant M. tuberculosis in AFB-negative sputum was 90.00% (95% CI, 55.46% to 98.34%), and specificity was 91.94% (95% CI, 82.16% to 97.30%). Compared to GeneXpert, the reporter phage was more sensitive in AFB smear-negative sputum, but specificity was lower. The Φ(2)GFP10 reporter phage showed high sensitivity for detection of M. tuberculosis and RIF resistance, including in AFB-negative sputum, and has the potential to improve phenotypic testing for complex drug resistance, paucibacillary sputum, response to treatment, and detection of mixed infection in clinical specimens.

USA's expanded overseas tuberculosis screening program: a retrospective study in China.

BackgroundTo address increasing tuberculosis (TB) incidence in foreign-born populations, immigrant TB screening programs have been implemented in the USA. These programs are modified periodically, the effectiveness of which have been disputed. The aim of this retrospective study was to assess the value of the 2009 Technical Instructions for Tuberculosis Screening and Treatment Using Cultures and Directly Observed Therapy (CDOT TB TI) in a cohort of the USA permanent-resident applicants from China.MethodsStandardized forms were used to collect demographic, clinical, and laboratory data of Chinese individuals screened at the Guangdong International Travel Healthcare Center for permanent residence in the USA between October 08, 2009 and December 31, 2012. Applicants’ data were further retrospectively evaluated by three experienced panel physicians and radiologists according to the 1991 Technical Instructions for Tuberculosis Screening and Treatment (TI). TB cases and characteristics identified by the 1991 and expanded 2009 programs were compared.ResultsThe CDOT TB TI identified more than twice as many TB cases that required treatment completion before clearance for travel than the 1991 TI (270 vs. 131). In addition, the expanded screening program identified more cases of negative sputum smear but positive culture (181 vs. 44), and more cases of radiography suggestive of inactive (22 vs. 3) and active (248 vs. 128) TB. Specifically, the 1991 TI screening program failed to identify 25/38 (65.79%) cases carrying drug-resistant isolates, and 13/131 (9.92%) would have been inappropriately treated. Moreover, 220/270 (81.48%) of the cases were asymptomatic, which were identified by screening and subsequently treated. Improved chest radiograph and sputum negative conversion occurred in all treated cases.ConclusionCDOT TB TI, a screening program that includes sputum culture and drug susceptibility tests, identifies a greater number of TB cases, likely contributing to the overall decrease in TB prevalence in host (USA) and origin (China) countries.

Spontaneous and induced sputum values in the diagnosis of pulmonary tuberculosis among patients with suspected pulmonary tuberculosis

Objectives: The quality of sputum samples is important for the diagnosis of pulmonary tuberculosis (TB). Unfortunately, it is not always possible to get a proper sputum sample. Now, sputum induction (SI) has been found to be useful for the diagnosis of many lung diseases. Therefore, this study compares the role of spontaneous sputum and induced sputum in the diagnosis of pulmonary TB among suspected pulmonary TB patients. Materials and Methods: A total of 27 patients admitted with suspected pulmonary TB were studied. Three spontaneous sputum samples were taken from these patients and in case of negative sputum smear microscopy, the SI procedure was used to take another sputum sample. Standard diagnosis included both positive sputum smear and clinical decisions. The sensitivity, specificity, and positive and negative predictive values of sputum smears obtained by two methods of spontaneous sputum and induced sputum were calculated and compared with the standard diagnosis. Results: The result of the induced sputum acid-fast bacillus (AFB) smear microscopy was negative in 16 (59.3%) patients and positive in 11 (40.7%) patients. Six (50%) of those who were negative in spontaneous sputum became positive after SI. The mean white blood cell (WBC) count in normal sputum and induced sputum was 3.8 (±3.4) and 8.8 (±2.9), respectively (P < 0.001). The sensitivity of sputum smear positive was calculated to be 67.7% for SI method and 29.4% for spontaneous sputum method. Conclusion: The diagnostic value of induced sputum in the diagnosis of TB is more than the spontaneous sputum method. In addition, the quality of sputum smear produced through induction is more than spontaneous sputum and it does not create any special complication.

Comparison of Xpert MTB/RIF Assay and the Conventional Sputum Microscopy in Detecting Mycobacterium tuberculosis in Northern Thailand.

Background. Despite low sensitivity in detection of Mycobacterium tuberculosis, sputum acid-fast smear remains the main diagnostic method. This study aimed to compare the diagnostic performance of Xpert MTB/RIF assay versus conventional sputum acid-fast smear. Materials and Methods. A cross-sectional study was conducted at Chiang Mai University Hospital, Thailand. Patients who were ≥15 years old and had clinically suspected pulmonary tuberculosis were included. Results. 109 specimens from 57 patients were included. Using MGIT sputum culture as a reference standard, the sensitivity (SEN) and specificity (SPEC) for Xpert were 95.3% (95% CI, 84.2%, 99.4%) and 86.4% (95% CI, 75.7%, 93.6%). The SEN and SPEC for sputum acid-fast smear were 60.5% (95% CI, 44.4%, 75.0%) and 98.5% (95% CI, 91.8%, 100%). Xpert had significantly higher sensitivity (p value < 0.001) and lower specificity (p value = 0.022) than sputum acid-fast smear. Among 43 culture-proven M. tuberculosis specimens, sensitivity of Xpert was 100% (95% CI, 86.7%, 100%) in acid-fast positive smears (n = 26) and 88.2% (95% CI, 63.5%, 98.5%) in acid-fast negative smears (n = 17). Conclusions. The good sensitivity and specificity of Xpert assay in detecting M. tuberculosis from sputum specimens may help in early diagnosis and treatment of pulmonary tuberculosis, particularly among patients who had acid-fast negative sputum smear.

Implementing rapid testing for tuberculosis in Mozambique.

ProblemIn Mozambique, pulmonary tuberculosis is primarily diagnosed with sputum smear microscopy. However this method has low sensitivity, especially in people infected with human immunodeficiency virus (HIV). Patients are seldom tested for drug-resistant tuberculosis.ApproachThe national tuberculosis programme and Health Alliance International introduced rapid testing of smear-negative sputum samples. Samples were tested using a polymerase-chain-reaction-based assay that detects Mycobacterium tuberculosis deoxyribonucleic acid and a mutation indicating rifampicin resistance; Xpert® MTB/RIF (Xpert®). Four machines were deployed in four public hospitals along with a sputum transportation system to transfer samples from selected health centres. Laboratory technicians were trained to operate the machines and clinicians taught to interpret the results.Local settingIn 2012, Mozambique had an estimated 140 000 new tuberculosis cases, only 34% of which were diagnosed and treated. Of tuberculosis patients, 58% are HIV-infected.Relevant changesFrom 2012–2013, 1558 people were newly diagnosed with tuberculosis using sputum smears at intervention sites. Xpert® detected M. tuberculosis in an additional 1081 sputum smear-negative individuals, an increase of 69%. Rifampicin resistance was detected in 58/1081 (5%) of the samples. However, treatment was started in only 82% of patients diagnosed by microscopy and 67% of patients diagnosed with the rapid test. Twelve of 16 Xpert® modules failed calibration within 15 months of implementation.Lessons learntUsing rapid tests to diagnose tuberculosis is promising but logistically challenging. More affordable and durable platforms are needed. All patients diagnosed with tuberculosis need to start and complete treatment, including those who have drug resistant strains.

Tuberculosis in health care workers in Belarus.

Tuberculosis (TB), including drug-resistant TB, is a serious problem in Belarus. To determine the prevalence of TB among health care workers (HCWs) along with patient characteristics, treatment outcomes and drug resistance patterns between 2008 and 2012. A retrospective national record review. There were 116 HCWs with TB. Case notification rates were higher among HCWs than in the general population (349 vs. 40/100 000 in 2012). Most HCWs with TB were nurses (n = 46, 40%) or nurse assistants (n = 37, 32%), female (n = 100, 86%) and aged 25-44 years (n = 84, 72%). Most common places of work for HCWs with TB were multidrug-resistant (MDR-) and extensively drug-resistant (XDR-TB) wards (n = 23, 20%), general medical (n = 26, 22%) and non-medical (n = 34, 29%) departments. All HCWs had pulmonary TB, 107 (92%) had new TB and 103 (89%) had negative sputum smears. Of the 38 (33%) with culture and drug susceptibility testing (DST), 28 (74%) had MDR-/XDR-TB. In 109 HCWs evaluated for final treatment outcomes, 97 (89%) were successfully treated, and their results were not affected by DST status. This study highlights the high prevalence of recorded TB in HCWs in TB health facilities in Belarus: there is a need to better understand and rectify this problem.

A first insight into high prevalence of undiagnosed smear-negative pulmonary tuberculosis in Northern Ethiopian prisons: implications for greater investment and quality control.

BackgroundTuberculosis (TB) transmission in prisons poses significant risks to inmates as well as the general population. Currently, there are no data on smear-negative pulmonary TB cases in prisons and by extension no data on the impact such cases have on TB incidence. This study was designed to obtain initial data on the prevalence of smear-negative cases of TB in prisons as well as preliminary risk factor analysis for such TB cases.MethodsThis cross-sectional survey was conducted in November 2013 at eight main prisons located in the state of Amhara, Ethiopia. Interviews using a structured and pretested questionnaire were done first to identify symptomatic prisoners. Three consecutive sputum samples were collected and examined using acid fast bacilli (AFB) microscopy at the point of care. All smear-negative sputum samples were taken for culture and Xpert testing. Descriptive and multivariate analysis was done using SPSS version 16.ResultsOverall the prevalence of smear-negative pulmonary TB cases in the study prisons was 8% (16/200). Using multivariate analysis, a contact history to TB patients in prison, educational level, cough and night sweating were found to be predictors of TB positivity among smear-negative pulmonary TB cases (p≤ 0.05).ConclusionsIn the studied prisons, high prevalence of undiagnosed TB cases using AFB microscopy was documented, which is an important public health concern that urgently needs to be addressed. Furthermore, patients with night sweating, non-productive cough, a contact history with TB patients and who are illiterate merit special attention, larger studies are warranted in the future to assess the associations more precisely. Further studies are also needed to examine TB transmission dynamics by patients with smear-negative pulmonary TB in a prison setting.

Treatment delay affects clinical severity of tuberculosis: a longitudinal cohort study

ObjectivesTo describe the risk factors for treatment delay and the effect of delay on the severity of tuberculosis (TB) in a prospectively followed TB cohort at the Bandim Health Project...

Intensified Tuberculosis Case-Finding in HIV-Positive Adults Managed at Ethiopian Health Centers: Diagnostic Yield of Xpert MTB/RIF Compared with Smear Microscopy and Liquid Culture

BackgroundDetection of active tuberculosis (TB) before antiretroviral therapy (ART) initiation is important, but optimal diagnostic methods for use in resource-limited settings are lacking. We assessed the prevalence of TB, evaluated the diagnostic yield of Xpert MTB/RIF in comparison with smear microscopy and culture, and the impact of Xpert results on clinical management in HIV-positive adults eligible for ART at health centers in a region of Ethiopia.MethodsParticipants were prospectively recruited and followed up at 5 health centers. Trained nurses collected data on socio-demographic characteristics, medical history and symptoms, and performed physical examination. Two paired morning sputum samples were obtained, and lymph node aspirates in case of lymphadenopathy. Diagnostic yield of Xpert MTB/RIF in sputum was compared with smear microscopy and liquid culture.ResultsTB was diagnosed in 145/812 participants (17.9%), with bacteriological confirmation in 137 (16.9%). Among bacteriologically confirmed cases, 31 were smear-positive (22.6%), 96 were Xpert-positive (70.1%), and 123 were culture-positive (89.8%). Xpert MTB/RIF increased the TB detection rate by 64 cases (47.4%) compared with smear microscopy. The overall sensitivity of Xpert MTB/RIF was 66.4%, and was not significantly lower when testing one compared with two samples. While Xpert MTB/RIF was 46.7% sensitive among patients with CD4 cell counts >200 cells/mm3, this increased to 82.9% in those with CD4 cell counts ≤100 cells/mm3. Compared with Xpert-positive TB patients, Xpert-negative cases had less advanced HIV and TB disease characteristics.ConclusionsPreviously undiagnosed TB is common among HIV-positive individuals managed in Ethiopian health centers. Xpert MTB/RIF increased TB case detection, especially in patients with advanced immunosuppression. An algorithm based on the use of a single morning sputum sample for individuals with negative sputum smear microscopy could be considered for intensified case finding in patients eligible for ART. However, technical and cost-effectiveness issues relevant for low-income countries warrant further study.

Editorial Commentary: Molecular Laboratory Testing for Tuberculosis: Innovators, Early Adopters, or Laggards?

Despite the recent progress toward meeting the Millennium Development Goal target to halt and to reverse the tuberculosis epidemic by 2015, the global burden of tuberculosis remains significant. In 2012, there were an estimated 8.6 million new cases of tuberculosis and 1.3 million died from the disease—5 deaths every 2 minutes! Among these deaths, an estimated 170 000 were caused by multidrug-resistant (MDR) tuberculosis, a relatively high total compared with 450 000 incident MDR tuberculosis cases. Worldwide and in most countries with a high burden of MDR tuberculosis, less than one-third of the tuberculosis patients estimated to have MDR tuberculosis were actually detected in 2012 [1]. In 2012, a total of 9945 new tuberculosis cases were reported in the United States, representing a 5.4% decrease from 2011 and 62.7% decrease from 1992 when the tuberculosis resurgence peaked at 26 673 cases. While this is indeed an accomplishment, the fact that 17 states reported increased case counts from 2011 to 2012 is concerning. Primary MDR tuberculosis is reported in 1.1% of tuberculosis cases and fluctuated between 0.9% and 1.3%— stable but no progress. Thirty-one states reported ≥50% of tuberculosis cases in foreign-born persons and 11 states even reported≥70%. The top 5 countries of origin of foreign-born persons with tuberculosis during 2007–2012 were Mexico, the Philippines, India, Viet Nam, and China [2]. According to the World Health Organization (WHO), more than half of the global MDR tuberculosis cases are from India, China, and the Russian Federation [1]. Today, laboratory testing in the mycobacteriology field is experiencing more changes than ever before. Determining what assay will be most useful to the healthcare provider is a challenge, and rapid acceptance of the new technology by the medical community an even greater one. In August 2013, the US Food and Drug Administration permitted marketing of the Xpert MTB/RIF (Xpert) assay (Cepheid, Sunnyvale, California) to detect DNA of the Mycobacterium tuberculosis complex and genetic mutations associated with resistance to rifampin (RIF) in unprocessed sputum and concentrated sputum sediments. In this issue of Clinical Infectious Diseases, Sohn and colleagues [3] from the Montreal Chest Institute, Canada, evaluated the Xpert assay in a low-incidence, high-resource ambulatory setting, specifically, in a university hospital tuberculosis clinic for the detection of pulmonary tuberculosis on induced sputum samples, using mycobacterial cultures as the reference standard. During the duration of the study, 924 patients were evaluated for tuberculosis and 502 consecutive patients were enrolled in the study (most with abnormal chest radiographs; only 18% symptomatic). Reasons for not enrolling included language barrier and refusal of the patient. Four induced sputum samples were collected. The second samplewas subjected to the Xpert assay and the other 3 samples were sent to the clinical microbiology laboratory for acid-fast bacilli (AFB) smear microscopy and culture using one liquid medium (Mycobacterium Growth Indicator Tube, BD). If the AFB smear was positive, a reflex nucleic acid amplification test (NAAT) was performed. A NAAT was performed on AFB smear-negative sputum samples by request only. Xpert results were not made available for clinical decision making. Twenty-four subjects were identified with active tuberculosis by culture. Xpert had an overall sensitivity of 46% and a specificity of 100%. The sensitivity was 86% in the 7 AFB smear-positive subjects and 29% in the 18 AFB smearnegative, culture-positive subjects. Most participants with culture-positive tuberculosis had minimal disease: only 7 of 25 (28%) culture-positive subjects were AFB smear-positive, only 12 (44%) had symptoms at presentation, and 2 subjects Received 29 December 2013; accepted 07 January 2014. Correspondence: Max Salfinger, MD, Mycobacteriology Laboratory, K 420, National Jewish Health, 1400 Jackson St, Denver, CO 80206 (salfingerm@njhealth.org). Clinical Infectious Diseases © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals. permissions@oup.com. DOI: 10.1093/cid/ciu024

Miliary tuberculosis in an immunocompetent male

Introduction: Miliary tuberculosis (tb) is a disseminated form of tuberculosis which may involve the lungs and other organs. It is a rare but potentially lethal form of tuberculosis seen mostly in immunocompromised patients. It is, however, not commonly reported in immunocompetent hosts. case report: We present a case of a 67-year-old African-American male who presented with persistent non-productive cough for three weeks, diarrhea, fatigue and weight loss. there was no history of active tb contacts, HIV infection, or other predisposing factor for immunosuppression. Physical examination was also unremarkable. chest X-ray and computed tomography scan revealed bilateral extensive small nodular infiltrates with negative serial acid-fast sputum smears. Acid-fast bacilli were detected in sputum culture at four weeks and were identified by DNA probe as Mycobacterium tuberculosis. conclusion: Miliary tuberculosis is a potentially lethal form of tuberculosis that mostly affects immunosuppressed patients, although in rare occasions can also affect immunocompetent adults.

Effect of Relative Centrifugal Forces and Centrifugation Times on Recovery of Mycobacterium Tuberculosis

&lt;p&gt;&lt;strong&gt;Background:&lt;/strong&gt; Tuberculosis (TB) is one of the major cause of morbidity and mortality worldwide, affecting one third of world's population and the incidence is much higher in South-East Asia (India and China together account for nearly 40% of the global TB cases)&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objectives:&lt;/strong&gt; The current study was designed to evaluate the efficacy of relative centrifugal forces (RCFs) and various centrifugations times (CTs) on recovery of Mycobacterium tuberculosis (MTB) from sputum specimens pre-inoculated with MTB.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Materials and Methods:&lt;/strong&gt; For this study, direct acid fast bacilli (AFB) smear negative sputum specimens were randomly collected, which were further subjected to sterilization (by autoclaving at 121°C for 15 min) and then seeded with MTB. Afterwards, these sputum specimens were subjected to centrifugation (in a cold centrifuge) at various RCFs and CTs. After centrifugation, supernatants and sediments were inoculated on LJ media and incubated at 37°C with daily monitoring for 8 weeks.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results:&lt;/strong&gt; In the current study, as the RCFs (6000 × g) and CTs (25 min and 20 min) were increased, the growth detection time exponentially decreased (9 and 11 days) and culture grades (4+) were increased when cultured from the sediments. However, the recovery rates of MTB from the supernatant fluids were constantly decreased as RCFs and CTs increased.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion:&lt;/strong&gt; The current study concluded that a higher RCF of 6000 × g and CTs of 20 and 25 min could effectively detect the tubercle bacilli from the sputum specimens more efficiently than other lower RCFs and CTs.&lt;/p&gt;

Diagnostic accuracy and clinical role of rapid C-reactive protein testing in HIV-infected individuals with presumed tuberculosis in South Africa

To determine the accuracy and role of rapid C-reactive protein (CRP) testing in human immunodeficiency virus (HIV) infected individuals with presumed tuberculosis (TB). We enrolled HIV-infected adults (≥18 years)with a cough of ≥2 weeks and negative sputum smears for acid-fast bacilli in KwaZulu-Natal, South Africa. Participants were evaluated for pulmonary TB (PTB) by a nurse with rapid CRP, and independently by a physician by chest radiograph. Rapid CRP test results were compared with laboratory CRP and sputum sent for confirmation of TB. Among 93 participants, 55 (59%) were female, the mean age was 35 years, and the median CD4 count was 177/mm3. Forty-five (54%) participants were diagnosed with PTB. Diagnostic sensitivity and specificity were respectively 95% (95%CI 74–99) and 51%(95%CI 35–66) for rapid CRP >8 mg/l, 87% (95%CI 73–96) and 53% (95%CI 38–68) for nurse assessment, and 69% (95%CI 52–83) and 76% (95%CI 61–87) for physician examination. Combining a negative rapid CRP(≤8 mg/l) with nurse and physician assessments reduced the post-test probability of PTB from 22% to 6% and from 32% to 6%, respectively. Rapid CRP testing helped exclude PTB,and may be a valuable test in assisting nurses and physicians in TB-endemic regions.

Authors' reply: Serum Albumin for Tuberculosis in HIV Infected Patients Eligible for Antiretroviral Therapy.

We thank Professor Wiwanitkit for highlighting important aspects of hypoalbuminemia in HIV infected patients.1 Hypoalbuminaemia can be the result of inadequate protein intake, malabsorption, reduced production in the liver, increased catabolic state or increased excretion of proteins through the kidneys. In patients with chronic diseases such as cancer, tuberculosis or end stage renal disease, hypoalbuminemia can be explained by a reduced protein intake due to anorexia and by an increased catabolic state due to inflammation. However, recent evidence shows that hypoalbuminemia is more likely to be a marker of inflammation than a marker of malnutrition, and nutritional supplementation is unlikely to raise serum albumin levels.2 HIV infection produces chronic inflammation. Hence, HIV could be a cause of hypoalbuminemia and one could expect a correlation between serum albumin concentrations and CD4 cell counts. However, Sudfeld et al did not observe an association between serum albumin levels and changes in the CD4 cell counts, and the CD4 cell counts did not affect the value of serum albumin for predicting mortality.3 It is possible that hypoalbuminemia could be a marker of inflammation in HIV infected patients and could be used as a predictor of mortality independent of the CD4 cell count.4 Whether the inflammation is produced by HIV itself or by co-infections such as tuberculosis is a matter that deserves further research. The objective of our study was not to explain the causes of hypoalbuminemia in HIV infected patients, but to explore the usefulness of hypoalbuminemia as a predictor of tuberculosis.5 The vast majority of HIV infected patients with tuberculosis are living in low- and middle-income countries, where the smear microscopy of sputum is most of the time the only available highly specific diagnostic test.6 In our setting, three-quarters of patients diagnosed with tuberculosis had smear negative sputum.7 Even in settings where the Xpert RIF/MTB assay is available, empirical treatment is the rule.8,9 Our study suggested that serum albumin could be useful for clinicians working in resource-poor settings when facing smear-negative HIV infected patients with clinical suspicion of tuberculosis. Patients with hypoalbuminemia will be more likely to have tuberculosis. Patients with higher albumin concentrations are less likely to have tuberculosis and, if they have tuberculosis, they have a better prognosis. The final decision on whether to start anti-tuberculous therapy empirically should not be based solely on the concentration of serum albumin, and other information such as compatible symptoms, physical examination and chest radiography should be taken into account. In Figure 1 we present the hazard ratio and 95% confidence intervals for tuberculosis by serum albumin concentrations using restricted cubic splines (seven knots) and Cox regression. Fig. 1 The low cost of the assay and the general availability in health care facilities in resource-poor settings make serum albumin very interesting from a public health point of view. In particular, it could be useful to improve the sensitivity and specificity of the four-symptom screening strategy recommended by the World Health Organization for intensified case finding and isoniazid preventive therapy. However, we agree with Professor Wiwanitkit in that our study has important limitations. It is a retrospective study using routinely collected data in a setting without tuberculosis culture. Only patients who had the serum albumin measured at the time of antiretroviral therapy eligibility were included. Forty-three percent of patients did not have a measurement of the serum albumin and were excluded. Prospective studies are needed to confirm our findings.