Background. It is uncertain whether diabetes affects the risk of developing latent tuberculosis infection (LTBI) following exposure to Mycobacterium tuberculosis (Mtb). We assessed the relationship of diabetes or prediabetes and LTBI among close and household contacts (HHCs) of patients with active pulmonary tuberculosis (TB) disease in Addis Ababa, Ethiopia. Methods. In this cross-sectional study, we performed interferon-γ release assays, TB symptom screening, and point-of-care glycolated hemoglobin (HbA1c) testing among HHCs of active TB cases. Diabetes status was classified into diabetes (HbA1c ≥6.5% or self-reported diagnosis), prediabetes (5.7%-6.4%), and euglycemia (≤5.6%). Multivariable logistic regression was used to determine the association of diabetes with LTBI. Results. Among 597 study participants, 123 (21%) had dysglycemia including diabetes (n = 31) or prediabetes (n = 92); 423 (71%) participants were diagnosed with LTBI. Twelve of 31 (39%) HHCs with diabetes were previously undiagnosed with diabetes. The prevalence of LTBI among HHCs with diabetes, prediabetes, and euglycemia was 87% (27/31), 73% (67/92), and 69% (329/474), respectively. In multivariable analysis adjusted for age, sex, and HIV status, the odds of LTBI among HHCs with diabetes were 2.33 (95% confidence interval [CI], .76-7.08) times the odds of LTBI without diabetes. When assessing interaction with age, the association of diabetes and LTBI was robust among participants aged ≥40 years (adjusted odds ratio [aOR], 3.68 [95% CI, .77-17.6]) but not those <40 years (aOR, 1.15 [95% CI, .22-6.1]). Conclusions. HHCs with diabetes may be more likely to have LTBI than those with euglycemia. Further investigations are needed to assess mechanisms by which diabetes may increase risk of LTBI after Mtb exposure.
Objective. To better understand hospital infection control practices in Ethiopia.
Design. A cross-sectional evaluation of healthcare worker (HCW)knowledge, attitudes, and practices about hand hygiene and tuberculosis (TB) infection control measures.
Methods. An anonymous 76-item questionnaire was administered to HCWs at 2 university hospitals in Addis Ababa, Ethiopia. Knowledge items were scored as correct/incorrect. Attitude and practice items were assessed using a Likert scale.
Results. In total, 261 surveys were completed by physicians (51%) and nurses (49%). Fifty-one percent of respondents were male; mean age was 30 years. While hand hygiene knowledge was fair, self-reported practice was suboptimal. Physicians reported performing hand hygiene 7% and 48% before and after patient contact, respectively. Barriers for performing hand hygiene included lack of hand hygiene agents (77%), sinks (30%), and proper training (50%) as well as irritation and dryness (67%) caused by hand sanitizer made in accordance with the World Health Organization formulation. TB infection control knowledge was excellent (more than 90% correct). Most HCWs felt that they were at high risk for occupational acquisition of TB (71%) and that proper TB infection control can prevent nosocomial transmission (92%). Only 12% of HCWs regularly wore a mask when caring for TB patients. Only 8% of HCWs reported that masks were regularly available, and 76% cited a lack of infrastructure to isolate suspected/known TB patients.
Conclusions. Training HCWs about the importance and proper practice of hand hygiene along with improving hand sanitizer options may improve patient safety. Additionally, enhanced infrastructure is needed to improve TB infection control practices and allay HCW concerns about acquiring TB in the hospital.
Following large declines in tuberculosis transmission the United States, large-scale screening programs targeting low-risk healthcare workers are increasingly a source of false-positive results. We report a large cluster of presumed false-positive tuberculin skin test results in healthcare workers following a change to 50-dose vials of Tubersol tuberculin.
A major impediment to improving the health of communities is the lack of qualified clinical and translational research (CTR) investigators. To address this workforce shortage, the National Institutes of Health (NIH) developed mechanisms to enhance the career development of CTR physician, PhD, and other doctoral junior faculty scientists including the CTR-focused K12 program and, subsequently, the KL2-mentored CTR career development program supported through the Clinical and Translational Science Awards (CTSAs). Our evaluation explores the impact of the K12/KL2 program embedded within the Atlanta Clinical and Translational Science Institute (ACTSI), a consortium linking Emory University, Morehouse School of Medicine and the Georgia Institute of Technology. We conducted qualitative interviews with program participants to evaluate the impact of the program on career development and collected data on traditional metrics (number of grants, publications). 46 combined K12/KL2 scholars were supported between 2002 and 2016. 30 (65%) of the 46 K12/KL2 scholars are women; 24 (52%) of the trainees are minorities, including 10 (22%) scholars who are members of an underrepresented minority group. Scholars reported increased research skills, strong mentorship experiences, and positive impact on their career trajectory. Among the 43 scholars who have completed the program, 39 (91%) remain engaged in CTR and received over $89 000 000 as principal investigators on federally funded awards. The K12/KL2 funding provided the training and protected time for successful career development of CTR scientists. These data highlight the need for continued support for CTR training programs for junior faculty.
OBJECTIVES: To assess latent tuberculous infection (LTBI) treatment completion rates in a large prospective US/Canada multisite cohort and identify associated risk factors.
METHODS: This prospective cohort study assessed factors associated with LTBI treatment completion through interviews with persons who initiated treatment at 12 sites. Interviews were conducted at treatment initiation and completion/cessation. Participants received usual care according to each clinic’s procedure. Multivariable models were constructed based on stepwise assessment of potential predictors and interactions.
RESULTS: Of 1515 participants initiating LTBI treatment, 1323 had information available on treatment completion; 617 (46.6%) completed treatment. Baseline predictors of completion included male sex, foreign birth, not thinking it would be a problem to take anti-tuberculosis medication, and having health insurance. Participants in stable housing who received monthly appointment reminders were more likely to complete treatment than those without stable housing or without monthly reminders. End-of-treatment predictors of non-completion included severe symptoms and the inconvenience of clinic/pharmacy schedules, barriers to care and changes of residence. Common reasons for treatment non-completion were patient concerns about tolerability/toxicity, appointment conflicts, low prioritization of TB, and forgetfulness.
CONCLUSIONS: Less than half of treatment initiators completed treatment in our multisite study. Addressing tangible issues such as not having health insurance, toxicity concerns, and clinic accessibility could help to improve treatment completion rates.
S E T T I N G: Hawassa Prison, Southern Region of Ethiopia.
O B J E C T I V E: To determine the burden of pulmonary tuberculosis (TB) using active case finding among prisoners.
D E S I G N: In this cross-sectional study, prisoners were screened for TB using a symptom screen. Those with cough of 72 weeks had spot and morning sputum samples collected for acid-fast bacilli (AFB) smear microscopy and molecular diagnostic testing (Xpert w MTB/RIF).
R E S U LT S: Among 2068 prisoners, 372 (18%) had a positive cough screen. The median age of these 372 persons was 23 years, 97% were male and 63% were from urban areas. Among those with a positive symptom screen, 8 (2%) were AFB sputum smear-positive and 31 (8%) were Xpert-positive. The point prevalence of pulmonary TB at the prison was 1748 per 100 000 persons. In multivariate analysis, persons with cough .4 weeks were more likely to have TB (OR 3.34, 95%CI 1.54-7.23).
C O N C L U S I O N: A high prevalence of TB was detected among inmates at a large Ethiopian prison. Active case finding using a cough symptom screen in combination with Xpert had high utility, and has the potential to interrupt transmission of Mycobacterium tuberculosis in correctional facilities in low- and middle-income, high-burden countries.
Background. Given very limited data, we assessed the long-term outcomes among patients with extensively drug-resistant (XDR) tuberculosis (TB).
Methods. A retrospective population-based cohort study was performed in patients with XDR-TB diagnosed during 2011- 2013 in the country of Georgia. Data were abstracted from the National TB Program, medical charts, interviews, and the national Georgian death registry.
Results. Among 111 patients starting treatment for XDR-TB, 59 (53.2%) had newly diagnosed tuberculosis, and 3 (2.9%) had human immunodeficiency virus (HIV) coinfection. The median length of follow-up from diagnosis of XDR-TB to death or the end of study was 53.9 months (interquartile range, 27.2-66.3 months). End-of-treatment outcomes were available for 106 patients; 35 (33.0%) had a favorable outcome, and 71 (67.0%) had an unfavorable outcome, including death in 16 (15.1%). An additional 20 patients died after cessation of initial treatment, increasing the overall mortality rate to 34.0%. In multivariable analysis, an unfavorable initial end-of-treatment outcome was associated with posttreatment death (adjusted odds ratio, 14.41; 95% confidence interval, 1.78-117.13).
Conclusions. The overall mortality rate and specifically the posttreatment mortality rate were high among patients with XDR-TB. Patients with an unfavorable end-of-treatment outcome had an increased risk of death during follow-up. Our findings highlight the need for improved adherence, better-tolerated and shorter therapies, and enhanced posttreatment surveillance among patients treated for XDR-TB.
The country of Georgia has a high burden of multi- and extensively drug-resistant tuberculosis (XDR-TB). To evaluate whether mutations in gyrB and eis genes increased the sensitivity of detection of phenotypic resistance to ofloxacin and kanamycin or capreomycin compared to use of the first-generation MTBDRsl assay alone, which tests for mutations in gyrA and rrs genes, a retrospective study of stored Mycobacterium tuberculosis isolates was performed. All isolates underwent DNA sequencing of resistance-determining regions. Among 112 M. tuberculosis isolates with DNA extraction data, targeted sequencing was successfully performed for each gene as follows: for gyrA, 98% sensitivity; for gyrB, 96%; for rrs, 93%; for the eis gene and its promoter, 93%. The specificity and hence the positive predictive value of gyrA and gyrB mutations for detecting ofloxacin resistance were 100%. The addition of gyrB mutations increased the sensitivity of phenotypic ofloxacin resistance detection by 13% (75% to 88%). All rrs resistance-conferring mutations were A1401G, and this mutation had low sensitivity (40% and 18%) and high specificity (95% and 100%) in predicting phenotypic capreomycin and kanamycin resistance, respectively. The eis C-14T mutation increased the sensitivity of phenotypic kanamycin resistance detection by 9% (18% to 27%) and was found solely in kanamycin phenotypic resistance isolates. Our data showed that the inclusion of eis C-14T and gyrB mutations in addition to rrs and gyrA mutations improves the sensitivity of detection of phenotypic ofloxacin and kanamycin resistance, respectively.
SETTING: Tuberculosis (TB) health care facilities throughout Georgia.
OBJECTIVE: To describe smoking behaviors among health care workers (HCWs) at TB facilities and determine HCWs' knowledge and beliefs regarding the impact of tobacco use on anti-tuberculosis treatment.DESIGN: Cross-sectional survey from May to December 2014 in Georgia. Adult HCWs (age 718 years) at TB facilities were eligible. We administered a 60-question anonymous survey about tobacco use and knowledge of the effect of smoking on anti-tuberculosis treatment.
RESULTS: Of the 431 HCWs at TB facilities who participated, 377 (87.5%) were female; the median age was 50 years (range 20-77). Overall, 59 (13.7%) HCWs were current smokers and 35 (8.1%) were past smokers.Prevalence of current smoking was more common among physicians than among nurses (18.6% vs.7.9%, P , 0.0001). Among HCWs, 115 (26.7%) believed smoking does not impact anti-tuberculosis treatment, and only 25.3% of physicians/nurses received formal training in smoking cessation approaches.Physicians who smoked were significantly more likely to believe that smoking does not impact anti-tuberculosis treatment than non-smoking physicians (aOR 5.11, 95%CI 1.46-17.90).
CONCLUSION: Additional education about the effect of smoking on TB treatment outcomes is needed for staff of TB health care facilities in Georgia. Nurses and physicians need more training about smoking cessation approaches for patients with TB.
Improved knowledge regarding the tissue penetration of antituberculosis drugs may help optimize drug management. Patients with drug-resistant pulmonary tuberculosis undergoing adjunctive surgery were enrolled. Serial serum samples were collected, and microdialysis was performed using ex vivo lung tissue to measure pyrazinamide concentrations. Among 10 patients, the median pyrazinamide dose was 24.7 mg/kg of body weight. Imaging revealed predominant lung lesions as cavitary (n 6 patients), mass-like (n 3 patients), or consolidative (n 1 patient). On histopathology examination, all tissue samples had necrosis; eight had a pH of ≤5.5. Tissue samples from two patients were positive for Mycobacterium tuberculosis by culture (pH 5.5 and 7.2). All 10 patients had maximal serum pyrazinamide concentrations within the recommended range of 20 to 60μg/ml. The median lung tissue free pyrazinamide concentration was 20.96 μg/ml. The median tissue-To-serum pyrazinamide concentration ratio was 0.77 (range, 0.54 to 0.93). There was a significant inverse correlation between tissue pyrazinamide concentrations and the amounts of necrosis (R -0.66, P 0.04) and acid-fast bacilli (R -0.75, P 0.01) identified by histopathology. We found good penetration of pyrazinamide into lung tissue among patients with pulmonary tuberculosis with a variety of radiological lesion types. Our tissue pH results revealed that most lesions had a pH conducive to pyrazinamide activity. The tissue penetration of pyrazinamide highlights its importance in both drug-susceptible and drug-resistant antituberculosis treatment regimens.