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Lymphocyte-depleting induction lowers acute rejection (AR) rates among high-immunologic risk (HIR) renal transplant recipients, including African Americans (AAs), retransplants, and the sensitized. It is unclear whether different HIR subgroups experience similarly low rates of AR. We aimed to describe the incidence of AR and de novo donor-specific antibody (dnDSA) among HIR recipients categorized by age, race, or donor type. All received antithymocyte globulin (ATG) induction and triple maintenance immunosuppression. A total of 464 HIR recipients from 2007 to 2014 were reviewed. AR and dnDSA rates at 1 year for the entire population were 14% and 27%, respectively. AR ranged from 6.7% among living donor (LD) recipients to 30% in younger AA deceased donor (DD) recipients. De novo donor-specific antibody at 1 year ranged from 7% in older non-AA LD recipients to 32% in AAs. AA race remained as an independent risk factor for AR among DD recipients and for dnDSA among all HIR recipients. Development of both AR and dnDSA within the first year was associated with a 54% graft survival at 5 years and was an independent risk factor for graft loss. Despite utilization of recommended immunosuppression for HIR recipients, substantial disparities exist among subgroups, warranting further consideration of individualized immunosuppression in certain HIR subgroups., (© 2016 Steunstichting ESOT.)

Background: Screening for and treating tuberculosis (TB) infection in children and adolescents is an effective way of decreasing future TB cases. However, current approaches leave many children at risk for TB unidentified., Methods: We recruited adolescent students from 2 public high schools (a magnet and a low-income) in the Houston Independent School District. Compared with the magnet school, the student population at the low-income school was larger, primarily Hispanic and economically disadvantaged. Students were educated about TB, and parents completed a risk factor questionnaire. Students with TB risk factors were tested using 2 interferon gamma release assays (IGRAs). Those with a positive IGRA received a 12-dose regimen of weekly isoniazid/rifapentine (3HP) administered via direct observation at school., Results: Nine hundred twenty-five students received TB education; 73% of their parents submitted the TB questionnaire. Eighty-six percent of students (n = 415) with a TB risk factor identified on the study questionnaire agreed to IGRA testing. Sixteen students had at least one positive IGRA (1% [magnet], 4.1% [low-income]; P = 0.005). Recent student travel to a high-risk country (7) or contact with TB disease (2) were associated with IGRA positivity (P < 0.05). All students with a positive IGRA accepted, tolerated and completed 3HP treatment at school., Conclusions: School-based TB education, screening, testing using IGRAs and administration of 3HP treatment is feasible to improve the identification and treatment of adolescent students at risk for TB.

Mycobacterium tuberculosis, the causative agent of tuberculosis, is responsible for 1.5 million deaths annually. We previously showed that M. tuberculosis infection in mice induces expression of the CO-producing enzyme heme oxygenase (HO1) and that CO is sensed by M. tuberculosis to initiate a dormancy program. Further, mice deficient in HO1 succumb to M. tuberculosis infection more readily than do wild-type mice. Although mouse macrophages control intracellular M. tuberculosis infection through several mechanisms, such as NO synthase, the respiratory burst, acidification, and autophagy, how human macrophages control M. tuberculosis infection remains less well understood. In this article, we show that M. tuberculosis induces and colocalizes with HO1 in both mouse and human tuberculosis lesions in vivo, and that M. tuberculosis induces and colocalizes with HO1 during primary human macrophage infection in vitro. Surprisingly, we find that chemical inhibition of HO1 both reduces inflammatory cytokine production by human macrophages and restricts intracellular growth of mycobacteria. Thus, induction of HO1 by M. tuberculosis infection may be a mycobacterial virulence mechanism to enhance inflammation and bacterial growth., (Copyright © 2016 by The American Association of Immunologists, Inc.)

Objective: A population-based study of 135 multidrug-resistant tuberculosis (MDR-TB) patients reported to the Centers for Disease Control and Prevention (CDC) during 2005-2007 found 73% were hospitalized. We analyzed factors associated with hospitalization., Methods: We assessed statistically significant multivariable associations with US in-patient TB diagnosis, frequency of hospitalization, length of hospital stay, and in-patient direct costs to the health care system., Results: Of 98 hospitalized patients, 83 (85%) were foreign-born. Blacks, diabetics, or smokers were more likely, and patients with disseminated disease less likely, to receive their TB diagnosis while hospitalized. Patients aged ⩾65 years, those with the acquired immune-deficiency syndrome (AIDS), or with private insurance, were hospitalized more frequently. Excluding deaths, length of stay was greater for patients aged ⩾65 years, those with extensively drug-resistant TB (XDR-TB), those residing in Texas, those with AIDS, those who were unemployed, or those who had TB resistant to all first-line medications vs. others. Average hospitalization cost per XDR-TB patient (US$285 000) was 3.5 times that per MDR-TB patient (US$81 000), in 2010 dollars. Hospitalization episode costs for MDR-TB rank third highest and those for XDR-TB highest among the principal diagnoses., Conclusions: Hospitalization was common and remains a critical care component for patients who were older, had comorbidities, or required complex management due to XDR-TB. MDR-TB in-patient costs are among the highest for any disease.

Setting: An Hoa Clinic, a district-level human immunodeficiency virus (HIV) clinic in Ho Chi Minh City, Viet Nam., Objective: To assess the performance of chest radiograph (CXR) in screening for pulmonary tuberculosis (PTB) among HIV-infected individuals and identify misdiagnosed opportunities., Design: This cross-sectional study was conducted in 397 HIV-infected patients consecutively enrolled at the An Hoa Clinic in Ho Chi Minh City, Viet Nam, from August 2009 to June 2010. The performance of CXR in TB screening was assessed based on its sensitivity, specificity, positive likelihood ratio and negative likelihood ratio., Results: Symptom screening alone missed 50% of PTB cases. The combination of CXR and symptom screening yielded an additional 28.6% (8/28) in PTB screening as compared with symptom screening alone, and should be applied routinely, especially in high TB prevalent settings., Conclusion: CXR is a good predictor for PTB even in HIV-infected individuals. The combination of CXR and screening for common TB symptoms considerably improved the sensitivity of detecting active PTB in people living with HIV. If available, routine sputum culture and the World Health Organization-endorsed Xpert(®) MTB/RIF assay should be implemented to achieve a more accurate diagnosis.

Background. Acceptance of dual kidney transplantation (DKT) has proven difficult, due to surgical complexity and concerns regarding long-term outcomes. We herein present a standard technique for ipsilateral DKT and compare outcomes to single-kidney transplant (SKT) recipients. Methods. A retrospective single-center comparison of DKT and SKT performed between February 2007 and July 2013. Results. Of 516 deceased donor kidney transplants, 29 were DKT and 487 were SKT. Mean follow-up was 43 ± 67 months. DKT recipients were older and more likely than SKT recipients to receive an extended criteria graft (p < 0.001). For DKT versus SKT, the rates of delayed graft function (10.3 versus 9.2%) and acute rejection (20.7 versus 22.4%) were equivalent (p = ns). A higher than expected urologic complication rate in the DKT cohort (14 versus 2%, p < 0.01) was reduced through modification of the ureteral anastomosis. Graft survival was equivalent between DKT and SKT groups (p = ns) with actuarial 3-year DKT patient and graft survivals of 100% and 93%. At 3 years, the groups had similar renal function (p = ns). Conclusions. By utilizing extended criteria donor organs as DKT, the donor pool was enlarged while providing excellent patient and graft survival. The DKT urologic complication rate was reduced by modification of the ureteral anastomosis.

BK polyomavirus infection and de novo donor-human leukocyte antigen (HLA) specific antibodies (dnDSA) are two well-known and distinct complications occurring after kidney transplantation. Recent literature suggests an association between the two events. This study aims to examine the relationship between BK viremia (BKV) and dnDSA and to identify potential risk factors for dnDSA following BKV in kidney transplant recipients. A retrospective review of 1019 recipients from Houston Methodist Hospital was conducted. All patients underwent routine screening for BKV and dnDSA. Median follow-up was 44 months. BKV was detected in 186 (18%) patients at a median of 107 (82-205) days post-transplant. dnDSA occurred in 283 (28%) patients at a median of 272 (62-575) days post-transplant. Of the 69 dnDSA-positive/BKV-positive patients, dnDSA detection occurred after BKV onset in 46 patients. Thus, 46 (28%) previously DSA-negative patients later became dnDSA-positive following BKV, not significantly different from the rate seen in BKV-negative patients (26%; p=0.5). Median time to DSA detection following BKV onset was 232 days (interquartile range, 119-460) post-BKV detection. Multivariate analysis revealed a greater number of HLA mismatches and viral clearance as risk factors for development of dnDSA following BKV, whereas delayed graft function was associated with a lower risk of dnDSA. In conclusion, despite being considered a result of over-immunosuppression, BKV can still be followed by dnDSA in a substantial proportion of patients. Monitoring for dnDSA in patients being managed for BKV may be warranted., (Copyright© 2017 by the Terasaki Research Institute.)

Background: Non-steroidal anti-inflammatory drugs are considered potentially harmful for patients with heart failure., Objective: To determine the prevalence of in-hospital NSAID use, their type, associated diagnosis and impact in clinical outcomes among patients with a diagnosis of heart failure., Methods: The University Health System Consortium Database was used to identify all first hospitalizations with an International Classification of Diseases-9 discharge diagnosis code of systolic heart failure as the primary diagnosis between January 1, 2011, and December 31st 2014., Results: Among 65,902 patients admitted for a primary diagnosis of SHF, 2675 (4.1%) were exposed to NSAID. The most frequent NSAID used was ibuprofen (51.63%), followed by ketorolac (29.38%) naproxen (8.07%) celecoxib (5.61%), and others. On multivariable analyses, the length of stay of patients exposed to NSAID was longer compared to non-exposed (OR: 4.67, p < 0.001, 95% CI 4.10-5.25), but differences in mortality were not statistically different (OR: 0.90, p = 0.476, 95% CI 0.69-1.19)., Conclusion: The use of NSAID in patients admitted with a primary diagnosis of systolic heart failure was low but was associated with longer length of stay. Further studies are needed to understand the impact of NSAID use in this patient population.

Background: The Xpert MTB/RIF (MTB/RIF) test has advanced the field of tuberculosis (TB) diagnostics; however, depending on age and HIV status, 10-85% of individuals with presumed pulmonary TB (PTB) are unable to produce sputum., Methods: The feasibility of using MTB/RIF and culture on stool and string test specimens from 13 adult patients with presumed PTB was studied., Results: The string test was well tolerated with a median Wong Baker Faces score of 2. The string test had 100% sensitivity and specificity by MTB/RIF and 87.5% sensitivity and 100% specificity by culture. In stool, Mycobacterium tuberculosis DNA was detected in all cases of culture-confirmed PTB., Conclusion: The string test and stool provide diagnostic specimens that warrant further investigation., (Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The objective of this study was to examine prevalence and clinical implications of subclinical coronary artery disease (CAD) detected by coronary artery calcium score (CACS) testing in patients with atrial fibrillation (AF). CACS was assessed in patients without history of CAD undergoing catheter ablation of AF. Age- and gender-matched patients with normal sinus rhythm (NSR) presenting with chest pain served as controls. Predicted arterial age using the Multi-Ethnic Study of Atherosclerosis registry was also compared to the chronologic age. A total of 860 patients (430 AF and 430 NSR, age 63 ± 10 years, 65% men) were included. Subclinical CAD prevalence (CACS >0) was 74% (319 of 430) in the AF group. Compared to the patients with NSR, patients with AF had higher prevalence of Subclinical CAD (74% vs 63%; p <0.001). In multivariate analysis, AF was independently associated with Subclinical CAD (hazard ratio 1.60; p = 0.002) but only with persistent AF (hazard ratio 2.28; p <0.001). Predicted arterial age was greater than chronologic age in patients with AF (69 ± 12 vs 64 ± 9 years). CACS-diagnosed subclinical CAD identified new potential candidates for statin therapy (12%; 33 of 267) and for oral anticoagulation (19%; 40 of 206) by addition of subclinical CAD to the CHA2DS2-VASc scores. In conclusion, in patients without known history of CAD, prevalence of subclinical CAD was significantly higher in those with persistent AF than those with NSR. AF was associated with subclinical CAD independently and complimentarily to clinical risk factors. Identifying subclinical CAD has potential clinical indications for prevention of CAD progression and stroke., (Copyright © 2015 Elsevier Inc. All rights reserved.)

BSL3 and respiratory isolation wards protect healthcare workers from nosocomial TB infection in China http://ow.ly/PGvSl., Competing Interests: Conflicts of Interest: None declared.

Objective: To investigate incidence and timing, risk factors, prognostic significance, and electrophysiological mechanisms of atrial arrhythmia (AA) after lung transplantation., Background: Although new-onset AA is common after thoracic surgery and is associated with poorer outcomes, prognostic and mechanistic data is sparse in lung transplant populations., Method: A total of 293 consecutive isolated lung transplant recipients without known AA were retrospectively reviewed. Mean follow-up was 28±17 months. Electrophysiology studies (EPS) were performed in 25 patients with AA., Results: The highest incidence of new-onset AA after lung transplantation occurred within 30 days postoperative AA, (25 % of all patients). In multivariable analysis, postoperative AA was associated with double lung transplantation (OR 2.79; p=0.005) and lower mean pulmonary artery pressure (OR 0.95; p=0.027). Patients with postoperative AA had longer hospital stays (21 days vs 12 days; p<0.001). Postoperative AA was independently associated with late AA (HR 13.52; p<0.001) but not mortality (HR 1.55; p=0.14). In EPS, there were 14 patients with atrial flutter alone and 11 with atrial flutter and fibrillation. Of all EPS patients, 20 (80%) had multiple AA mechanisms, including peritricuspid flutter (48%), perimitral flutter (36%), right atrial incisional reentry (24%), focal tachycardia from recipient pulmonary vein (PV) antrum (32 %), focal PV fibrillation (24%), and left atrial roof flutter (20%). Left atrial mechanisms were present in 80% (20/25) of EPS patients and originated from the anastomotic PV antrum., Conclusions: Postoperative AA was independently associated with longer length of stay and late AA but not mortality. Pleomorphic PV antral arrhythmogenesis from native PV antrum is the main cause of AA after lung transplantation.

Unlabelled: Overweight-mortality paradox and impact of six-minute walk distance (SMWD) in lung transplantation., Background: The objective of this study was to examine combined prognostic influence of body mass index (BMI) and SMWD on mortality in lung transplant recipients., Methods: Consecutive isolated lung transplant recipients were identified. Preoperative BMI and SMWD data were collected. The cohort was followed for all-cause mortality., Results: The study included 324 lung transplant recipients with mean age of 57 ± 13 years and 58% were male (27% obstructive, 3% vascular, 6% cystic fibrosis, and 64% with restrictive lung diseases). In the total cohort; 37% had normal BMI, 10% were underweight, 33% were overweight, and 20% were obese. The median SMWD was 700 feet. The lower SMWDgroup was defined as the patients who had SMWD <237 feet as determined by receiver operating characteristic (ROC). Based on this definition, 66 patients (20%) had lower SMWD. There were 71 deaths during a median follow-up of 2.3 years. In multivariate analysis, both BMI and SMWD were independently associated with death. Being overweight was associated with reduced mortality risk (hazard ratio (HR) 0.50, P = 0.042) compared to the normal BMI group, and this was primarily driven by early mortality posttransplant. This paradoxical overweight-mortality relationship remained significant in the lower SMWD group (HR 0.075, P = 0.018), but not in the higher SMWD group (P = 0.552)., Conclusion: In lung transplant recipients under lung allocation score (LAS) era, pretransplant BMI and SMWD were independent predictors for mortality after the transplant. The lowest mortality risk was noted in a group of transplant recipients identified as overweight; whereas, being underweight or obese was associated with increased mortality.

Background: Preemptive transplantation results in excellent patient and graft survival yet most transplant candidates are referred for transplantation after initiation of dialysis. The goal of this study was to determine barriers to preemptive renal transplantation., Methods: A nonvalidated questionnaire was administered to prospective kidney transplant recipients to determine factors that hindered or favored referral for transplantation before the initiation of dialysis., Results: One hundred ninety-seven subjects referred for a primary renal transplant completed the questionnaire. Ninety-one subjects (46%) had been informed of preemptive transplantation before referral, and 80 (41%) were predialysis at the time of evaluation. The median time from diagnosis of renal disease to referral was 60 months (range, 2-444 months). In bivariate analysis, among other factors, knowledge of preemptive transplantation was highly associated (odds ratio=94.69) with referral before initiation of dialysis. Given the strong association between knowledge of preemptive transplantation and predialysis referral, this variable was not included in the multivariate analysis. Using multivariate logistic regression analysis, white recipient race, referral by a transplant nephrologist, recipient employment, and the diagnosis of polycystic kidney disease were significantly associated with presentation to the pretransplant clinic before initiation of dialysis., Conclusion: The principle barrier to renal transplantation referral before dialysis was patient education regarding the option of preemptive transplantation. Factors significantly associated with referral before dialysis were the diagnosis of polycystic kidney disease, white recipient race, referral by a transplant nephrologist, and employed status. Greater effort should be applied to patient education regarding preemptive transplantation early after the diagnosis of end-stage renal disease.

Interferon gamma release assays (IGRAs) are poorly studied in HIV-infected children. The authors prospectively evaluated QuantiFERON-TB Gold results and family-described tuberculosis (TB) risk factors in 100 HIV-infected children in Botswana. Median age was 10.2 years; 58 were girls, 92 had received the Bacillus Calmette-Guérin (BCG) vaccine, 98 were receiving antiretroviral therapy, and the median body mass index was 15.8 kg/m(2). Eighty-nine children had undetectable viral loads and the median CD4 count was 962 cells/mm(3). Eighteen children had been treated for TB in the last 3 years. In the last 3 years, 36 (including 9 with TB) had contact with persons with TB (26 within/15 outside the home and 5 had >1 contact). In all, 96 children had negative IGRAs, 3 were indeterminate, and 1 was positive. The positive IGRA was reported in a child treated for TB prior to 3 years. Interferon γ release assay positivity was rare in this pediatric cohort living in an area with a high prevalence of TB., (© The Author(s) 2014.)

Background: Centers for Disease Control and Prevention requirements for pre-immigration tuberculosis (TB) screening of children 2- to 14-years old permit a tuberculin skin test (TST) or an interferon-gamma release assay (IGRA). Few data are available on the performance of IGRAs versus TSTs in foreign-born children., Methods: We compared the performance of TST and QuantiFERON-TB (QFT) Gold In-Tube in children 2- to 14-years old applying to immigrate to the United States from Mexico, the Philippines and Vietnam, using diagnosis of TB in immigrating family members as a measure of potential exposure., Results: We enrolled 2520 children: 664 (26%) were TST+ and 142 (5.6%) were QFT+. One hundred and eleven (4.4%) were TST+/QFT+, 553 (21.9%) were TST+/QFT- and 31 (1.2%) were TST-/QFT+. Agreement between tests was poor (κ = 0.20). Although positive results of both tests were significantly associated with older age (relative risks [RR] TST+, 1.64; 95% confidence interval [CI]: 1.36-1.97; RR QFT+, 3.05; 95% CI: 1.72-5.38) and with the presence of TB in at least 1 immigrating family member (RR TST+, 1.40; 95% CI: 1.12-1.75; RR QFT+ 2.24; 95% CI: 1.18-4.28), QFT+ results were more strongly associated with both predictive variables., Conclusions: The findings support the preferential use of QFT over TST for pre-immigration screening of foreign-born children 2 years of age and older and lend support to the preferential use of IGRAs in testing foreign-born children for latent TB infection., Competing Interests: Research was funded by the Centers for Disease Control and Prevention, Tuberculosis Epidemiologic Studies Consortium. The authors have no conflicts of interest or financial relationships relevant to this manuscript to disclose.

Rationale: HIV-associated tuberculosis remains a major health problem among the gold-mining workforce in South Africa. We postulate that high levels of recent transmission, indicated by strain clustering, are fueling the tuberculosis epidemic among gold miners., Objectives: To combine molecular and epidemiologic data to describe Mycobacterium tuberculosis genetic diversity, estimate levels of transmission, and examine risk factors for clustering., Methods: We conducted a cross-sectional study of culture-positive M. tuberculosis isolates in 15 gold mine shafts across three provinces in South Africa. All isolates were subject IS6110-based restriction fragment length polymorphisms, and we performed spoligotyping analysis and combined it with basic demographic and clinical information., Measurements and Main Results: Of the 1,602 M. tuberculosis patient isolates, 1,240 (78%) had genotyping data available for analysis. A highly diverse bacillary population was identified, comprising a total of 730 discrete genotypes. Four genotypic families (Latin American Mediterranean spoligotype family; W-Beijing; AH or X; and T1-T4) accounted for over 50% of all strains. Overall, 45% (560/1,240) of strains were genotypically clustered. The minimum estimate for recent transmission (n - 1 method) was 32% (range, 27-34%). There were no individual-level risk factors for clustering, apart from borderline evidence for being non-South African and having self-reported HIV infection., Conclusions: The high M. tuberculosis genetic diversity and lack of risk factors for clustering are indicative of a universal risk for disease among gold miners and likely mixing with nonmining populations. Our results underscore the urgent need to intensify interventions to interrupt transmission across the entire gold-mining workforce in South Africa.

Current methods for the detection of Mycobacterium tuberculosis (Mtb) are either time consuming or require expensive instruments and are thus are not suitable for point-of-care diagnosis. The design, synthesis, and evaluation of fluorogenic probes with high specificity for BlaC, a biomarker expressed by Mtb, are described. The fluorogenic probe CDG-3 is based on cephalosporin with substitutions at the 2 and 7 positions and it demonstrates over 120,000-fold selectivity for BlaC over TEM-1 Bla, the most common β-lactamase. CDG-3 can detect 10 colony-forming units of the attenuated Mycobacterium bovis strain BCG in human sputum in the presence of high levels of contaminating β-lactamases expressed by other clinically prevalent bacterial strains. In a trial with 50 clinical samples, CDG-3 detected tuberculosis with 90% sensitivity and 73% specificity relative to Mtb culture within one hour, thus demonstrating its potential as a low-cost point-of-care test for use in resource-limited areas., (© 2014 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.)

To describe factors associated with multidrug-resistant (MDR), including extensively-drug-resistant (XDR), tuberculosis (TB) in the United States, we abstracted inpatient, laboratory, and public health clinic records of a sample of MDR TB patients reported to the Centers for Disease Control and Prevention from California, New York City, and Texas during 2005-2007. At initial diagnosis, MDR TB was detected in 94% of 130 MDR TB patients and XDR TB in 80% of 5 XDR TB patients. Mutually exclusive resistance was 4% XDR, 17% pre-XDR, 24% total first-line resistance, 43% isoniazid/rifampin/rifabutin-plus-other resistance, and 13% isoniazid/rifampin/rifabutin-only resistance. Nearly three-quarters of patients were hospitalized, 78% completed treatment, and 9% died during treatment. Direct costs, mostly covered by the public sector, averaged $134,000 per MDR TB and $430,000 per XDR TB patient; in comparison, estimated cost per non-MDR TB patient is $17,000. Drug resistance was extensive, care was complex, treatment completion rates were high, and treatment was expensive.

Background: Renal transplant recipients with de novo DSA (dDSA) experience higher rates of rejection and worse graft survival than dDSA-free recipients. This study presents a single-center review of dDSA monitoring in a large, multi-ethnic cohort of renal transplant recipients., Methods: The authors performed a nested case-control study of adult kidney and kidney-pancreas recipients from July 2007 through July 2011. Cases were defined as dDSA-positive whereas controls were all DSA-negative transplant recipients. DSA were determined at 1, 3, 6, 9, and 12 months posttransplant, and every 6 months thereafter., Results: Of 503 recipients in the analysis, 24% developed a dDSA, of whom 73% had dDSA against DQ antigen. Median time to dDSA was 6.1 months (range 0.2-44.6 months). After multivariate analysis, African American race, kidney-pancreas recipient, and increasing numbers of human leukocyte antigen mismatches were independent risk factors for dDSA. Recipients with dDSA were more likely to suffer an acute rejection (AR) (35% vs. 10%, P<0.001), an antibody-mediated AR (16% vs. 0.3%, P<0.001), an AR ascribed to noncompliance (8% vs. 2%, P=0.001), and a recurrent AR (6% vs. 1%, P=0.002) than dDSA-negative recipients. At a median follow-up of 31 months, the death-censored actuarial graft survival of dDSA recipients was worse than the DSA-free cohort (P=0.002). Yet, for AR-free recipients, there was no difference in graft survival between cohorts (P=0.66)., Conclusions: Development of dDSA was associated with an increased incidence of graft loss, yet the detrimental effect of dDSA was limited in the intermediate term to recipients with AR.

The isolation of Mycobacterium tuberculosis from blood culture specimens has been associated with human immunodeficiency virus (HIV) co-infection with variable impact on tuberculosis (TB) mortality reported. The overwhelming majority of M. tuberculosis bacteraemia cases were described in developing countries. We present a nested case-control analysis of clinical, sociodemographic and behavioural risk factors in patients with positive M. tuberculosis blood cultures compared with patients with negative blood cultures from a 9-year population-based active TB surveillance study conducted in Houston, Texas. There were 42 patients with M. tuberculosis bacteraemia, 47 blood culture negative patients and 3573 patients for whom no mycobacterial blood culture was requested. HIV infection was more common in patients for whom a mycobacterial blood culture was requested (79.8% versus 15.1% p <0.001). Of the patients with M. tuberculosis bacteraemia, six were HIV negative or had no documentation of HIV status, including five with immunosuppressive conditions other than HIV. Patients with M. tuberculosis bacteraemia were more likely than patients with negative blood cultures to be deceased at diagnosis or to die while on TB therapy (50.0% versus 17.0%, p <0.01), to report men-who-have-sex-with-men behaviour (31.7% versus 13.0%, p 0.03), to have renal failure (28.6% versus 6.4%, p 0.01), and to have HIV RNA levels higher than 500 000 copies/mL (61.9% versus 17.2%, p ≤0.01). Requests for mycobacterial culture of blood specimens were more common in HIV-infected individuals, and the presence of M. tuberculosis bacteraemia was associated with a significant increase in mortality., (© 2013 The Authors Clinical Microbiology and Infection © 2013 European Society of Clinical Microbiology and Infectious Diseases.)

Context: A prototype miniature objective that was designed for a point-of-care diagnostic array microscope for detection of Mycobacterium tuberculosis and previously fabricated and presented in a proof of concept is evaluated for its effectiveness in detecting acid-fast bacteria., Objective: To evaluate the ability of the microscope to resolve submicron features and details in the image of acid-fast microorganisms stained with a fluorescent dye, and to evaluate the accuracy of clinical diagnoses made with digital images acquired with the objective., Design: The lens prescription data for the microscope design are presented. A test platform is built by combining parts of a standard microscope, a prototype objective, and a digital single-lens reflex camera. Counts of acid-fast bacteria made with the prototype objective are compared to counts obtained with a standard microscope over matched fields of view. Two sets of 20 smears, positive and negative, are diagnosed by 2 pathologists as sputum smear positive or sputum smear negative, using both a standard clinical microscope and the prototype objective under evaluation. The results are compared to a reference diagnosis of the same sample., Results: More bacteria are counted in matched fields of view in digital images taken with the prototype objective than with the standard clinical microscope. All diagnostic results are found to be highly concordant., Conclusions: An array microscope built with this miniature lens design will be able to detect M tuberculosis with high sensitivity and specificity.

Objectives: To estimate tuberculosis (TB) rates among young children in the United States by children's and parents' birth origins and describe the epidemiology of TB among young children who are foreign-born or have at least 1 foreign-born parent., Methods: Study subjects were children <5 years old diagnosed with TB in 20 US jurisdictions during 2005-2006. TB rates were calculated from jurisdictions' TB case counts and American Community Survey population estimates. An observational study collected demographics, immigration and travel histories, and clinical and source case details from parental interviews and health department and TB surveillance records., Results: Compared with TB rates among US-born children with US-born parents, rates were 32 times higher in foreign-born children and 6 times higher in US-born children with foreign-born parents. Most TB cases (53%) were among the 29% of children who were US born with foreign-born parents. In the observational study, US-born children with foreign-born parents were more likely than foreign-born children to be infants (30% vs. 7%), Hispanic (73% vs. 37%), diagnosed through contact tracing (40% vs. 7%), and have an identified source case (61% vs. 19%); two-thirds of children were exposed in the United States., Conclusions: Young children who are US born of foreign-born parents have relatively high rates of TB and account for most cases in this age group. Prompt diagnosis and treatment of adult source cases, effective contact investigations prioritizing young contacts, and targeted testing and treatment of latent TB infection are necessary to reduce TB morbidity in this population., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.

Rapid screening and diagnosis of tuberculosis disease (TB) is still challenging and critically needed for global TB control efforts. In this study, we present a rapid and streamlined technology, using precisely engineered silica nanopore thin films, which are optimized for pore size, structure, capillary force, and film thickness, to isolate Mycobacterium tuberculosis (MTB) antigens in laboratory and clinical samples for rapid TB screening. This technology, referred to here as on-chip fractionation, is integrated with high-throughput matrix-assisted laser desorption/ionization time-of flight mass spectrometry to screen and identify fragments of the MTB antigen, CFP-10, from complex biological samples, without use of immunoaffinity agents. With the use of this comprehensive approach, we were able to clearly distinguish a clinical isolate of MTB from a nonTB species of the genus Mycobacterium avium grown in liquid culture media. This assay can reach a detection limit of 10 fmol and an isolation rate of 90% for the antigen CFP-10. Our strategy has significant potential to fill the conceptual and technical gaps in rapid diagnosis of active TB disease.

Fifty-six of 182 (31%) children had indeterminate QuantiFERON assays. Indeterminate assays were associated with inpatient status [odds ratios (OR): 11.7, 95% confidence interval 3.9-34.9], but not with age, gender or medical comorbidities. This indicates that indeterminates may be due to specimen handling, and proper procedural training may be necessary to decrease indeterminate QuantiFERON results.

Rationale: IFN-γ release assays (IGRAs) are alternatives to tuberculin skin testing (TST) for diagnosis of latent tuberculosis infection. Limited data suggest IGRAs may not perform well for serial testing of healthcare workers (HCWs)., Objectives: Determine the performance characteristics of IGRAs versus TST for serial testing of HCWs., Methods: A longitudinal study involving 2,563 HCWs undergoing occupational tuberculosis screening at four healthcare institutions in the United States, where the average tuberculosis case rate ranged from 4 to 9 per 100,000 persons. QuantiFERON-TB Gold In-Tube (QFT-GIT), T-SPOT.TB (T-SPOT), and TST were performed at baseline and every 6 months for 18 months between February 2008 and March 2011., Measurements and Main Results: A total of 2,418 HCWs completed baseline testing, which was positive for 125 (5.2%) by TST, 118 (4.9%) by QFT-GIT, and 144 (6.0%) by T-SPOT. A baseline positive TST with negative IGRAs was associated with bacillus Calmette-Guérin (BCG) vaccination (odds ratio: 25.1 [95% confidence interval: 15.5, 40.5] vs. no BCG). Proportions of participants with test conversion during the study period were 138 of 2,263 (6.1%) for QFT-GIT, 177 of 2,137 (8.3%) for T-SPOT, and 21 of 2,293 (0.9%) for TST (P < 0.001 for QFT-GIT vs. TST and for T-SPOT vs. TST; P = 0.005 for QFT-GIT vs. T-SPOT). Of the QFT-GIT and T-SPOT converters, 81 of 106 (76.4%) and 91 of 118 (77.1%), respectively, were negative when retested 6 months later. There was negative/positive discordance for 15 of 170 (8.8%) participants by QFT-GIT and for 19 of 151 (12.6%) by T-SPOT when blood was drawn 2 weeks later., Conclusions: Most conversions among HCWs in low TB incidence settings appear to be false positives, and these occurred six to nine times more frequently with IGRAs than TST; repeat testing of apparent converters is warranted.

Rationale: Each year 1 million persons acquire permanent U.S. residency visas after tuberculosis (TB) screening. Most applicants undergo a 2-stage screening with tuberculin skin test (TST) followed by CXR only if TST-positive at > 5 mm. Due to cross reaction with bacillus Calmette-Guérin (BCG), TST may yield false positive results in BCG-vaccinated persons. Interferon gamma release assays exclude antigens found in BCG. In Vietnam, like most high TB-prevalence countries, there is universal BCG vaccination at birth., Objectives: 1. Compare the sensitivity of QuantiFERON-TB Gold In-Tube Assay (QFT) and TST for culture-positive pulmonary TB. 2. Compare the age-specific and overall prevalence of positive TST and QFT among applicants with normal and abnormal CXR., Methods: We obtained TST and QFT results on 996 applicants with abnormal CXR, of whom 132 had TB, and 479 with normal CXR., Results: The sensitivity for tuberculosis was 86.4% for QFT; 89.4%, 81.1%, and 52.3% for TST at 5, 10, and 15 mm. The estimated prevalence of positive results at age 15-19 years was 22% and 42% for QFT and TST at 10 mm, respectively. The prevalence increased thereafter by 0.7% year of age for TST and 2.1% for QFT, the latter being more consistent with the increase in TB among applicants., Conclusions: During 2-stage screening, QFT is as sensitive as TST in detecting TB with fewer requiring CXR and being diagnosed with LTBI. These data support the use of QFT over TST in this population.

Tuberculosis genotypic clustering is used as a proxy for recent transmission. The association between clustering and recent transmission becomes problematic when the genotyping method lacks specificity in defining a cluster, as well as for clusters with extensive jurisdictional histories and/or common genotypes. We investigated the four largest spoligotype/12 loci MIRU-VNTR-defined clusters in Harris County, Texas from 2006-2012 to determine their historical contribution to tuberculosis morbidity, estimate the contributions from recent and remote transmission, and determine the impact of secondary genotyping on cluster definition. The clusters contained 189, 64, 51 and 38 cases. Each cluster was linked to cluster(s) previously identified by Houston Tuberculosis Initiative; 3 since 1995 and the fourth in 2002. Among cases for which timing of Mycobacterium tuberculosis transmission relative to tuberculosis disease could be ascertained, nearly equal proportions were associated with recent and remote transmission. The extent to which genotyping with an additional 12 MIRU-VNTR loci modified the cluster definition varied from little or no impact for the two smaller clusters to moderate impact for the larger clusters. Tuberculosis control measures to reduce morbidity associated with large clusters must involve strategies to identify and treat individuals who recently acquired infection, as well as persons infected for years., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: Multidrug-resistant (MDR) tuberculosis is a potential threat to tuberculosis elimination, but the extent of MDR tuberculosis disease in the USA that is attributable to transmission within the country is unknown. We assessed transmission of MDR tuberculosis and potential contributing factors in the USA., Methods: In a cross-sectional study, clinical, demographic, epidemiological, and Mycobacterium tuberculosis genotype data were obtained during routine surveillance of all verified cases of MDR tuberculosis reported from eight states in the USA (California from Jan 1, 2007, to Dec 31, 2009; Texas from Jan 1, 2007, to March 31, 2009; and the states of Colorado, Maryland, Massachusetts, New York, Tennessee, and Washington from Jan 1, 2007 to Dec 31, 2008). In-depth interviews and health-record abstraction were done for all who consented to ascertain potential interpersonal connections., Findings: 168 cases of MDR tuberculosis were reported in the eight states during our study period. 92 individuals (55%) consented to in-depth interview. 20 (22%) of these individuals developed MDR tuberculosis as a result of transmission in the USA; a source case was identified for eight of them (9%). 20 individuals (22%) had imported active tuberculosis (ie, culture-confirmed disease within 3 months of entry into the USA). 38 (41%) were deemed to have reactivation of disease, of whom 14 (15%) had a known previous episode of tuberculosis outside the USA. Five individuals (5%) had documented treatment of a previous episode in the USA, and so were deemed to have relapsed. For nine cases (10%), insufficient evidence was available to definitively classify reason for presentation., Interpretation: About a fifth of cases of MDR tuberculosis in the USA can be linked to transmission within the country. Many individuals acquire MDR tuberculosis before entry into the USA. MDR tuberculosis needs to be diagnosed rapidly to reduce potential infectious periods, and clinicians should consider latent tuberculosis infection treatment-tailored to the results of drug susceptibility testing of the putative source case-for exposed individuals., Funding: Centers for Disease Control and Prevention., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Objective: This study aimed to assess kidney dysfunction in general surgical patients and examine the effect on postoperative mortality and morbidity., Background: An estimated 13% of the US population has chronic kidney disease (CKD), but awareness among patients and caregivers is lacking., Methods: The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) data sets for 2005-2007 were analyzed. Preoperative kidney function was assessed by the Modification of Diet in Renal Disease formula for estimated glomerular filtration rate (eGFR) and staged according to National Kidney Foundation. Cross-sectional analyses were performed for 30-day mortality (Cox proportional hazard) and incidence of major complications (nominal logistic regression). A case-control cohort of colectomy cases was analyzed comparing patients in the stage 4 CKD group and the no CKD group (no-CKD)., Results: Sixty-four percent of evaluable patients had reduced eGFR, but eGFR was not evaluable in 28% of the surgical cases. In the 260,352 evaluable cases, adjusted hazard ratio for 30-day mortality was 2.30 [95% confidence interval (CI), 2.11-2.51] for stage 3 CKD; 3.37 (95% CI, 3.01-3.76) for stage 4 CKD; and 3.05 (95% CI, 2.68-3.47) for stage 5 CKD compared with no-CKD (P < 0.0001). CKD was an independent risk factor for having major complications postsurgery [stage 3, odds ratio (OR) = 1.24 (95% CI, 1.19-1.29); stage 4, OR = 1.65 (95% CI, 1.52-1.78); and stage 5 CKD, OR = 1.40 (95% CI, 1.30-1.51); P < 0.0001]. The case-control for colectomy was confirmatory: increased 30-day mortality in stage 4 CKD versus no-CKD (hazard ratio = 2.58, 95% CI, 1.13-5.92; P = 0.025)., Conclusions: Renal insufficiency may be underrecognized in the general and vascular (noncardiac) surgery population, is a leading independent predictor of poor early postoperative outcomes, and should be routinely assessed in the preoperative setting.

Background: Isoniazid-resistant (INHr) Mycobacterium tuberculosis isolates often have katG mutations, and katG is a virulence factor in animal models. It is unclear if katG mutations or other mutations influence the characteristics of human disease., Objective: To determine if the presence of INHr-conferring mutations were associated with distinct clinical features of tuberculosis (TB)., Methods: In a retrospective case-control study, INHr-conferring mutations were determined by DNA sequencing. We examined associations between clinical characteristics in patients with INHr M. tuberculosis (stratified by groups of relevant INHr-conferring mutations, including katG-S315T and inhA-C(-)15T mutations) and pan-susceptible (PS) isolates., Results: Twenty-nine INHr TB cases and 50 PS controls were evaluated. Disease characteristics were not statistically different between INHr and PS cases. However, patients infected with non-katG mutants were associated with a higher rate of sputum culture conversion at 1 month after adjustment for relevant covariates (adjusted OR [aOR] 4.4, 95%CI 1.1-23.6, P = 0.04). Patients infected with katG mutants were associated with a higher rate of unilateral disease (aOR 4.7, 95%CI 1.0-34.3, P = 0.05)., Conclusions: Most INHr TB cases with non-katG mutations have disease associated with faster response to treatment, and most cases with katG mutants have localized lung involvement.

Tuberculosis (TB) surveillance among the homeless is not supported by the political will necessary for TB elimination. We merged the first stakeholder-accepted enumeration of homeless persons with existing surveillance data to assess TB risk among the homeless in Houston, Texas. The average incidence per 100,000 was 411 among homeless and 9.5 among housed persons. The homeless were more likely than the housed to be US-born, clustered, and in a larger-sized cluster. Multivariate analysis revealed that TB rates among the homeless were driven not by comorbidities but by social determinants. Homeless patients were hospitalized more days than the housed and required more follow-up time. Reporting of TB rates for populations with known health disparities could help reframe TB prevention and better target limited funds.

Cytokines play an essential role during active tuberculosis disease and cytokine genes have been described in association with altered cytokine levels. Therefore, the aim of this study was to verify if IFNG, IL12B, TNF, IL17A, IL10, and TGFB1 gene polymorphisms influence the immune response of Brazilian patients with pulmonary tuberculosis (PTB) at different time points of antituberculosis treatment (T1, T2, and T3). Our results showed the following associations: IFNG +874 T allele and IFNG +2109 A allele with higher IFN- γ levels; IL12B +1188 C allele with higher IL-12 levels; TNF -308 A allele with higher TNF- α plasma levels in controls and mRNA levels in PTB patients at T1; IL17A A allele at rs7747909 with higher IL-17 levels; IL10 -819 T allele with higher IL-10 levels; and TGFB1 +29 CC genotype higher TGF- β plasma levels in PTB patients at T2. The present study suggests that IFNG +874T/A, IFNG +2109A/G, IL12B +1188A/C, IL10 -819C/T, and TGFB1 +21C/T are associated with differential cytokine levels in pulmonary tuberculosis patients and may play a role in the initiation and maintenance of acquired cellular immunity to tuberculosis and in the outcome of the active disease while on antituberculosis treatment.

Background: The epidemiology of pediatric tuberculosis (TB) from 1995 to 2000 in Harris County, TX, has been previously reported. This study was conducted to evaluate the continued trends of Mycobacterium tuberculosis clustering and the role of genotyping in pediatric TB., Methods: Data came from the Houston Tuberculosis Initiative, a prospective population-based active surveillance and molecular epidemiology project. The study population consisted of TB patients ≤18 years of age diagnosed in Harris County, TX, from 2000 to 2004. Available Mycobacterium tuberculosis isolates were characterized by insertion sequence 6110 restriction fragment length polymorphism and spoligotyping., Results: One hundred three pediatric TB cases were enrolled in the Houston Tuberculosis Initiative study from 2000 to 2004. Sixty-one (59%) patients had potential source cases. Mycobacterium tuberculosis isolates were available and genotyped for 36 pediatric cases; 27 (75%) were clustered into 22 different genotypes. Of the 20 genotyped patients with a potential source case, 16 (80%) were clustered. Genotypes matched the potential source case in 12 cases. Eleven of the 16 (69%) genotyped patients without a potential source case were clustered., Conclusions: Compared with pediatric cases between 1995 and 2000, there was a significant increase in the number of patients with unknown potential source cases that were clustered within the Houston Tuberculosis Initiative database. Because genotypic clustering is associated with recent transmission, there appears to be a failure in the identification of potential source cases through contact tracing. Reduced funding of public health departments forces more limited TB control activities and therefore could pose a threat to TB control.

Treatment failure of methicillin-resistant Staphylococcus aureus (MRSA) remains an important concern. In order to investigate new MRSA treatment modalities, we used standard time-kill assays to determine the in vitro killing rate of 22 strains of MRSA by vancomycin, telavancin, daptomycin, and ceftaroline. Studies were carried out with 7-10-times the minimum bactericidal concentrations of each antibiotic in broth culture for 24 h, with subculture at 4, 8, and 24 h. We found that killing by ceftaroline closely paralleled that of vancomycin. Telavancin killed bacteria significantly more slowly, whereas daptomycin killed significantly more rapidly.

Objectives: Trimethoprim/sulfamethoxazole effectively treats community-acquired soft tissue infections and urinary tract infections, both of which occur in patients with risk factors for renal impairment. We systematically studied the adverse renal effects of trimethoprim/sulfamethoxazole in a middle-aged veteran population., Methods: We reviewed complete electronic records for all patients who, during a 3 year period, had received ≥6 days of treatment with trimethoprim/sulfamethoxazole and for whom a baseline and follow-up determination of serum creatinine and blood urea nitrogen (BUN) were available., Results: Of 573 patients who met inclusion criteria, 64 (11.2%) had increases in both serum creatinine and BUN that met predetermined criteria for acute kidney injury (AKI): in 33 (5.8%), AKI was judged likely due to trimethoprim/sulfamethoxazole; in 28 (4.9%), possibly due to trimethoprim/sulfamethoxazole; and in 3 (0.52%), unrelated to trimethoprim/sulfamethoxazole. Five additional patients (0.9%) had elevations only in serum creatinine. In nearly all cases likely due to trimethoprim/sulfamethoxazole, AKI resolved promptly after discontinuation of therapy, but one patient required dialysis. Pyuria appeared in only 2 of 37 patients who had urinalyses; eosinophiluria was not observed. In a multivariate model, patients with hypertension and diabetes mellitus had increased risk for renal insufficiency, especially if these conditions were considered poorly controlled., Conclusions: In a middle-aged male inpatient population treated for a minimum of 6 days, AKI is much more common with trimethoprim/sulfamethoxazole therapy than previously reported. Intrinsic renal impairment rather than interstitial nephritis or competition for creatinine clearance appears responsible for the great majority of cases, and neither an effect of dose nor duration was detected in a univariate analysis. Impairment is transient if therapy is discontinued.

To investigate the prevalence of extensively drug-resistant tuberculosis (XDR-TB) in Chinese populations, we analyzed the drug resistance profiles of 1787 Mycobacterium tuberculosis isolates through a population-based surveillance project in Shandong Province, China. We found 330 (18.5%; 95%CI 16.1-20.3) isolates resistant to ≥1 first-line drug and 65 (3.6%; 95%CI 2.9-4.6) multidrug-resistant (MDR) isolates, of which 13 (20.0%; 95%CI 11.9-31.4) were XDR; 47/65 MDR-TB isolates (70.8%; 95%CI 58.2-81.4) were resistant to fluoroquinolones. Our results indicate that inadequate application of second-line anti-tuberculosis drugs has caused increased prevalence of XDR-TB in certain Chinese populations.

The interferon-gamma (IFN-γ) release assay (IGRA) is an in vitro extension of the century-old in vivo tuberculin skin test, better known as the TST. Shortcomings to the TST are multifactorial and include limitations in sensitivity and specificity. IGRAs improve diagnostic specificity by using antigens not found in the Bacille Calmette-Guérin, a vaccine given in most countries. IGRAs capture the IFN-γ produced by T cells in response to antigen stimulation. The ELISPOT immediately captures IFN-γ produced directly from each cell, resulting in the generation of a cellular "footprint." The dimensions and intensity of the generated footprint indicate the avidity of the secreting cell. We show a further improvement in IGRAs by addition of interleukin-7 (IL-7). IL-7 reduces T-cell apoptosis and stabilizes IFN-γ message. In addition to increasing the number of spots in the ELISPOT T-SPOT.TB platform, IL-7 increased IFN-γ production per cell as measured by an increase in spot size with no change in spot distribution.

Background. Tuberculosis (TB) disease diagnosis in Vietnam relies on symptom screening, chest radiography (CXR), and acid fast bacilli (AFB) sputum smear which have a poor sensitivity in HIV patients. We evaluated the performance of clinical algorithms in screening and diagnosing AFB smear-negative TB in HIV patients. Methods. We enrolled 399 HIV-positive patients seeking care at a HIV clinic in Ho Chi Minh City (HCMC), Vietnam. Participants' demographics, medical history, common TB symptoms, CXR, and laboratory tests were collected. Results. Of 399 HIV patients, 390 had initial AFB-negative smears and 22/390 patients had positive cultures. Symptom screening missed 54% (12/22) of smear-negative pulmonary TB (PTB) cases. Multivariate analysis found CD4+ cell level and CXR were significant PTB predictors. An algorithm combining four TB symptoms and TST presented a high sensitivity (100%), but poorly specific (24%) diagnostic performance for smear-negative PTB. Conclusion. Up to 54% of PTB cases in the HIV-infected population may be missed in the routine screening and diagnostic procedures used in Vietnam. Symptom screening was a poor overall diagnostic measure in detecting smear-negative TB in HIV patients. Our study results suggest that routine sputum cultures should be implemented to achieve a more accurate diagnosis of TB in HIV patients.

To reach the tuberculosis (TB) elimination goals established by the Institute of Medicine (IOM) and the Centers for Disease Control and Prevention (CDC), measures must be taken to speed the currently stagnant TB elimination rate and curtail a future peak in TB incidence. Increases in TB incidence have historically coincided with immigration, poverty, and joblessness; all situations that are currently occurring worldwide. Effective TB elimination strategies will require the geographical elucidation of areas within the U.S. that have endemic TB, and systematic surveillance of the locations and location-based risk factors associated with TB transmission. Surveillance data was used to assess the spatial distribution of cases, the yearly TB incidence by census tract, and the statistical significance of case clustering. The analysis revealed that there are neighborhoods within Houston/Harris County that had a heavy TB burden. The maximum yearly incidence varied from 245/100,000-754/100,000 and was not exclusively dependent of the number of cases reported. Geographically weighted regression identified risk factors associated with the spatial distribution of cases such as: poverty, age, Black race, and foreign birth. Public transportation was also associated with the spatial distribution of cases and census tracts identified as high incidence were found to be irregularly clustered within communities of varied SES., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

This paper describes the development of a microscope array capable of imaging separate fields of view without the need for opto-mechanical scanning components. This microscope array can be integrated with array illuminating optics, a full frame digital single lens reflex (DSLR) camera, and automated algorithms for the detection of Mycobacterium tuberculosis (MTB). The entire array will fit within the area of a typical sputum smear. A custom miniature objective has been designed for this microscope array that has a numerical aperture of 0.5, optical resolution of 0.63 μm, and a field of view that is 0.54 mm in diameter. A single prototype miniature objective of this design has been built, and images are presented demonstrating its imaging performance. Images are sufficiently high quality for diagnostic use. When fully integrated, this device has the potential to significantly improve performance compared to conventional microscopy systems and to enable more effective diagnosis of tuberculosis at the point of care., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Previous geospatial analysis of the well-defined Houston Tuberculosis Initiative (HTI) database identified an association between the use of city-bus transportation (inclusive of time onboard) and Tuberculosis (TB) incidence in Houston/Harris County census tracts (paper submitted). This paper is an extension of those findings. Contact investigations on school buses have reported a high rate of positive tuberculin skin tests in the persons traveling with the index case and have shown an association with bus ride duration. In Houston, city bus routes are veins connecting even the most diverse of populations within the metropolitan area. Among HTI participants, TB patients who reported weekly bus use were more likely to have demographic and social risk factors associated with poverty, immune suppression and health disparities. An equal proportion of bus riders and non-bus riders were cultured for Mycobacterium tuberculosis (MTB), yet 75% of bus riders were clustered with a mean cluster size of 50.14, indicating recent transmission, compared to 56% of non-bus riders (OR = 2.4, p < 0.001) with a mean cluster size of 28.9 (p < 0.01). Individual bus routes, including one route servicing the local hospitals, were found to be risk factors for endemic MTB clustered strains and the routes themselves geographically connect the census tracts previously identified as having endemic TB., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Setting: District 6, An Hoa Clinic in Ho Chi Minh City (HCMC), Viet Nam., Objective: To evaluate the performance of various algorithms in tuberculosis (TB) screening and diagnosis in a human immunodeficiency virus (HIV) infected population in HCMC, Viet Nam., Design: A cross-sectional study of 397 consecutive HIV-infected patients seeking care at the An Hoa Clinic from August 2009 to June 2010. Data on participant demographics, clinical status, chest radiography (CXR) and laboratory results were collected. A multiple logistic regression model was developed to assess the association of covariates and pulmonary TB (PTB)., Results: The prevalence of sputum culture-confirmed PTB, acid-fast bacilli (AFB) positive TB, and multidrugresistant TB among the 397 HIV-infected patients was respectively 7%, 2%, and 0.3%. Adjusted odds ratios for low CD4+ cell count, positive sputum smear, and CXR to positive sputum culture were respectively 3.17, 32.04 and 4.28. Clinical findings alone had poor sensitivity, but combining CD4+ cell count, AFB sputum smear and CXR had a more accurate diagnostic performance., Conclusion: Results suggest that symptom screening had poor clinical performance, and support the routine use of sputum culture to improve the detection of TB disease in HIV-infected individuals in Viet Nam. However, when routine sputum culture is not available, an algorithm combining CD4+ cell count, AFB sputum smear and CXR is recommended for diagnosing PTB.

Background: Intracranial tuberculomas are rare manifestations of tuberculosis (TB). An extensive literature review revealed that no study of consecutive adults with intracranial tuberculoma has been conducted in the USA., Methods: This retrospective study consisted of 12 adults consecutively identified with intracranial tuberculomas from 1995 to 2009 in Houston, Texas. Of the 12 cases, 8 had a histopathological diagnosis, while 4 had a probable diagnosis based on the following criteria: (1) Mycobacterium tuberculosis identified from a source outside the brain, (2) radiographic confirmation of an intracranial mass, (3) received chemotherapy with 2 or more anti-tuberculosis medications, and (4) clinical response at 1-y follow-up., Results: Common clinical manifestations were altered mental status, fever, and night sweats. Four patients (25%) had a human immunodeficiency virus (HIV) infection. Nine patients (75%) had concomitant M. tuberculosis at at least 1 extracranial site, including 5 patients with pulmonary TB. The median duration of therapy was 11 months. Patients had a 1-y mortality rate of 16.7% and an overall morbidity rate of 20%., Conclusions: Intracranial tuberculomas in Houston, Texas, are rare. Hospital discharge predicted survival at 1 y, despite severe clinical presentations and invasive diagnostic procedures. However, tuberculoma cases are associated with higher mortality rates than non-central nervous system TB cases.

Comprehensive data on the prevalence of quinolone resistance in Mycobacterium tuberculosis clinical isolates in the United States are scarce. By use of a systematic population-based approach, M. tuberculosis strains from tuberculosis (TB) cases were collected in Harris County, TX, in 2007 to 2008. The susceptibilities of M. tuberculosis isolates to moxifloxacin and ofloxacin were determined by the agar proportion indirect susceptibility method. Spoligotyping and 12-locus mycobacterial interspersed repetitive unit (MIRU12)-based genotyping of M. tuberculosis isolates were performed, and the gyrA, gyrB, Rv2686c, Rv2687c, and Rv2688c genes in quinolone-resistant and year-of-diagnosis-matched M. tuberculosis isolates were sequenced. Susceptibility testing was performed on 557 M. tuberculosis isolates, of which 10 (1.8%) were resistant to moxifloxacin. There was 100% concordance between ofloxacin and moxifloxacin susceptibilities. A quinolone was prescribed to at least 5 (50%) patients in the period preceding TB diagnosis. Multidrug-resistant TB (MDR-TB) was significantly associated with quinolone resistance (P = 0.01). Mutations in the quinolone resistance-determining region of gyrA were found for 50% of the resistant isolates. No other presumptive quinolone resistance-associated mutations were identified. We conclude that the incidence of moxifloxacin-resistant TB is low in Harris County and is associated with MDR-TB. Previous exposure to quinolones is common among patients with moxifloxacin resistance and warrants more careful evaluation.

To estimate the prevalence of extensively drug-resistant tuberculosis (XDR TB) in China, we retrospectively analyzed drug-resistance profiles of 989 clinical Mycobacterium tuberculosis isolates. We found 319 (32.3%) isolates resistant to ≥1 first-line drugs; 107 (10.8%) isolates were multidrug resistant, of which 20 (18.7%) were XDR. XDR TB is of major concern in China.

Regulatory T cells (Tregs) blunt uncontrolled immune responses. In advanced human immunodeficiency virus (HIV) infection, the total number of Tregs is decreased, but the proportion of T cells with a regulatory phenotype is highly variable. We studied CD4(+)CD25(+)FoxP3(+) T cells from patients successfully treated with combination antiretroviral therapy (ART). The proportion of CD4(+)CD25(+)FoxP3(+) cells transiently increased and then decreased from a median of 13% at baseline to 5.1% at 48 weeks, similar to values in normal subjects. These data suggest that with effective therapy, the regulatory cell numbers normalize, and that the inflammatory signals driving their production may also abate.

An ancestral polymorphic allele of the human autophagy-related gene IRGM1 is associated with altered gene expression and a genetic risk for Crohn's Disease (CD). We used the single nucleotide polymorphism rs10065172C/T as a marker of this polymorphic allele and genotyped 370 African American and 177 Caucasian tuberculosis (TB) cases and 180 African American and 110 Caucasian controls. Among African Americans, the TB cases were more likely to carry the CD-related T allele of rs10065172 (odds ratio of 1.54; 95% confidence interval, 1.17-2.02; P<0.01) compared to controls. Our finding suggests that this CD-related IRGM1 polymorphic allele is also associated with human susceptibility to TB disease among African Americans.