Last data update: May 06, 2024. (Total: 46732 publications since 2009)
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Query Trace: Bozeman L[original query] |
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Outbreak linked to morel mushroom exposure - Montana, 2023
Demorest H , Hinnenkamp R , Cook-Shimanek M , Troeschel AN , Yeh M , Hallett TC , Kuai D , Daniel J , Winquist A . MMWR Morb Mortal Wkly Rep 2024 73 (10) 219-224 During March-April 2023, a total of 51 persons reported mild to severe gastrointestinal illness after eating at restaurant A in Bozeman, Montana. The outbreak resulted in multiple severe outcomes, including three hospitalizations and two deaths. After an inspection and temporary restaurant closure, the Montana Department of Public Health and Human Services and Montana's Gallatin City-County Health Department collaborated with CDC to conduct a matched case-control study among restaurant patrons to help identify the source of the outbreak. Consumption of morel mushrooms, which are generally considered edible, was strongly associated with gastrointestinal illness. A dose-response relationship was identified, and consumption of raw morel mushrooms was more strongly associated with illness than was consumption of those that were at least partially cooked. In response to the outbreak, educational public messaging regarding morel mushroom preparation and safety was shared through multiple media sources. The investigation highlights the importance of prompt cross-agency communication and collaboration, the utility of epidemiologic studies in foodborne disease outbreak investigations, and the need for additional research about the impact of morel mushroom consumption on human health. Although the toxins in morel mushrooms that might cause illness are not fully understood, proper preparation procedures, including thorough cooking, might help to limit adverse health effects. |
High-dose rifapentine with or without moxifloxacin for shortening treatment of pulmonary tuberculosis: Study protocol for TBTC study 31/ACTG A5349 phase 3 clinical trial
Dorman SE , Nahid P , Kurbatova EV , Goldberg SV , Bozeman L , Burman WJ , Chang KC , Chen M , Cotton M , Dooley KE , Engle M , Feng PJ , Fletcher CV , Ha P , Heilig CM , Johnson JL , Lessem E , Metchock B , Miro JM , Nhung NV , Pettit AC , Phillips PPJ , Podany AT , Purfield AE , Robergeau K , Samaneka W , Scott NA , Sizemore E , Vernon A , Weiner M , Swindells S , Chaisson RE . Contemp Clin Trials 2020 90 105938 INTRODUCTION: Phase 2 clinical trials of tuberculosis treatment have shown that once-daily regimens in which rifampin is replaced by high dose rifapentine have potent antimicrobial activity that may be sufficient to shorten overall treatment duration. Herein we describe the design of an ongoing phase 3 clinical trial testing the hypothesis that once-daily regimens containing high dose rifapentine in combination with other anti-tuberculosis drugs administered for four months can achieve cure rates not worse than the conventional six-month treatment regimen. METHODS/DESIGN: S31/A5349 is a multicenter randomized controlled phase 3 non-inferiority trial that compares two four-month regimens with the standard six-month regimen for treating drug-susceptible pulmonary tuberculosis in HIV-negative and HIV-positive patients. Both of the four-month regimens contain high-dose rifapentine instead of rifampin, with ethambutol replaced by moxifloxacin in one regimen. All drugs are administered seven days per week, and under direct observation at least five days per week. The primary outcome is tuberculosis disease-free survival at twelve months after study treatment assignment. A total of 2500 participants will be randomized; this gives 90% power to show non-inferiority with a 6.6% margin of non-inferiority. DISCUSSION: This phase 3 trial formally tests the hypothesis that augmentation of rifamycin exposures can shorten tuberculosis treatment to four months. Trial design and standardized implementation optimize the likelihood of obtaining valid results. Results of this trial may have important implications for clinical management of tuberculosis at both individual and programmatic levels. TRIAL REGISTRATION: NCT02410772. Registered 8 April 2015,https://www.clinicaltrials.gov/ct2/show/NCT02410772?term=02410772&rank=1. |
Nonparticipation reasons in a randomized international trial of a new latent tuberculosis infection regimen
Hedges KNC , Borisov AS , Saukkonen JJ , Scott NA , Hecker EJ , Bozeman L , Dukes Hamilton C , Kerrigan A , Bessler P , Moreno-Martinez A , Arevalo B , Goldberg SV . Clin Trials 2019 17 (1) 1740774519885380 BACKGROUND/AIMS: Efficient recruitment of eligible participants, optimizing time and sample size, is a crucial component in conducting a successful clinical trial. Inefficient participant recruitment can impede study progress, consume staff time and resources, and limit quality and generalizability or the power to assess outcomes. Recruitment for disease prevention trials poses additional challenges because patients are asymptomatic. We evaluated candidates for a disease prevention trial to determine reasons for nonparticipation and to identify factors that can be addressed to improve recruitment efficiency. METHODS: During 2001-2009, the Tuberculosis Trials Consortium conducted Study 26 (PREVENT TB), a randomized clinical trial at 26 sites in four countries, among persons with latent tuberculosis infection at high risk for tuberculosis disease progression, comparing 3 months of directly observed once-weekly rifapentine plus isoniazid with 9 months of self-administered daily isoniazid. During March 2005-February 2008, non-identifying demographic information, risk factors for experiencing active tuberculosis disease, and reasons for not enrolling were collected from screened patients to facilitate interpretation of trial data, to meet Consolidated Standards of Reporting Trials standards, and to evaluate reasons for nonparticipation. RESULTS: Of the 7452 candidates screened in Brazil, Canada, Spain, and the United States, 3584 (48%) were not enrolled, because of ineligibility (41%), site decision (10%), or patient choice (49%). Among those who did not enroll by own choice, and for whom responses were recorded on whether they would accept treatment outside of the study (n = 1430), 68% reported that they planned to accept non-study latent tuberculosis infection treatment. Among 1305 patients with one or more reported reasons for nonparticipation, study staff recorded a total of 1886 individual reasons (reason count: median = 1/patient; range = 1-9) for why patients chose not to enroll, including grouped concerns about research (24% of 1886), work or school conflicts (20%), medication or health beliefs (16%), latent tuberculosis infection beliefs (11%), and patient lifestyle and family concerns (10%). CONCLUSION: Educational efforts addressing clinical research concerns and beliefs about medication and health, as well as study protocols that accommodate patient-related concerns (e.g. work, school, and lifestyle) might increase willingness to enter clinical trials. Findings from this evaluation can support development of communication and education materials for clinical trial sites at the beginning of a trial to allow study staff to address potential participant concerns during study screening. |
Factors associated with recruitment, surveillance participation, and retention in an observational study of pregnant women and influenza
Thompson MG , Li DK , Naleway AL , Ferber JR , Henninger ML , Shifflett P , Sokolow LZ , Odouli R , Kauffman TL , Fink RV , Bulkley J , Cragan JD , Bozeman S . BMC Pregnancy Childbirth 2019 19 (1) 161 BACKGROUND: This report describes the results of recruitment efforts and the subsequent participation of pregnant women in study activities in a 2010-2012 observational study focused on influenza illness and vaccination in California and Oregon, USA. METHODS: Socio-demographic and health characteristics extracted from electronic medical records were compared among pregnant women who enrolled in the study, refused to participate, or were never reached for study invitation. These characteristics plus additional self-reported information were compared between women who enrolled in two study tracks: a prospective cohort vs. women enrolled following an acute respiratory illness (ARI) medical encounter. The characteristics of women who participated in weekly ARI surveillance (cohort enrollees, year one) and a 6-month follow-up interview (all enrollees) were also examined. RESULTS: In year one, we reached 51% (6938/13,655) of the potential participants we tried to contact by telephone, and 20% (1374/6938) of the women we invited agreed to join the prospective cohort. Women with chronic medical conditions, pregnancy complications, and medical encounters for ARI (prior to pregnancy or during the study period) were more likely to be reached for recruitment and more likely to enroll in the cohort. Twenty percent of cohort enrollees never started weekly surveillance reports; among those who did, reports were completed for 55% of the surveillance weeks. Receipt of the influenza vaccine was higher among women who joined the cohort (76%) than those who refused (56%) or were never reached (54%). In contrast, vaccine uptake among medical enrollees in year one (54%; 53/98) and two (52%; 79/151) was similar to other pregnant women in those years. Study site, white race, non-Hispanic ethnicity, and not having a child aged < 13 years at home were most consistently associated with joining as a cohort or medical enrollee and completing study activities after joining. CONCLUSIONS: We observed systematic differences in socio-demographic and health characteristics across different levels of participant engagement and between cohort and medical enrollees. More methodological research and innovation in conducting prospective observational studies in this population are needed, especially when extended participant engagement and ongoing surveillance are required. |
Genetic Determinants of Drug Resistance in Mycobacterium tuberculosis and Their Diagnostic Value.
Farhat MR , Sultana R , Iartchouk O , Bozeman S , Galagan J , Sisk P , Stolte C , Nebenzahl-Guimaraes H , Jacobson K , Sloutsky A , Kaur D , Posey J , Kreiswirth BN , Kurepina N , Rigouts L , Streicher EM , Victor TC , Warren RM , van Soolingen D , Murray M . Am J Respir Crit Care Med 2016 194 (5) 621-30 BACKGROUND: The development of molecular diagnostics that detect both the presence of Mycobacterium tuberculosis in clinical samples and drug resistance-conferring mutations promises to revolutionize patient care and interrupt transmission by ensuring early diagnosis. However, these tools require the identification of genetic determinants of resistance to the full range of anti-tuberculosis drugs. OBJECTIVES: To determine the optimal molecular approach needed, we sought to create a comprehensive catalogue of resistance mutations and assess their sensitivity and specificity in diagnosing drug resistance. METHODS: We developed and validated molecular inversion probes for DNA capture and deep sequencing of 28 drug resistance loci in M.tuberculosis. We used the probes for targeted sequencing of a geographically diverse set of 1397 clinical M.tuberculosis isolates with known drug resistance phenotypes. We identified a minimal set of mutations to predict resistance to first- and second-line anti-tuberculosis drugs and validated our predictions in an independent dataset. We constructed and piloted a web-based database that provides public access to the sequence data and prediction tool. RESULTS: The predicted resistance to rifampicin and isoniazid exceeded 90% sensitivity and specificity, but was lower for other drugs. The number of mutations needed to diagnose resistance is large and for the 13 drugs studied it was 238 across 18 genetic loci. CONCLUSION: These data suggest that a comprehensive M.tuberculosis drug resistance diagnostic will need to allow for a high dimension of mutation detection. They also support the hypothesis that currently unknown genetic determinants, potentially discoverable by whole genome sequencing, encode resistance to second-line TB drugs. |
Effects of repeated annual inactivated influenza vaccination among healthcare personnel on serum hemagglutinin inhibition antibody response to A/Perth/16/2009 (H3N2)-like virus during 2010-11
Thompson MG , Naleway A , Fry AM , Ball S , Spencer SM , Reynolds S , Bozeman S , Levine M , Katz JM , Gaglani M . Vaccine 2016 34 (7) 981-8 BACKGROUND: Recently, lower estimates of influenza vaccine effectiveness (VE) against A(H3N2) virus illness among those vaccinated during the previous season or multiple seasons have been reported; however, it is unclear whether these effects are due to differences in immunogenicity. METHODS: We performed hemagglutination inhibition antibody (HI) assays on serum collected at preseason, approximately 30 days post-vaccination, and postseason from a prospective cohort of healthcare personnel (HCP). Eligible participants had medical and vaccination records for at least four years (since July, 2006), including 578 HCP who received 2010-11 trivalent inactivated influenza vaccine [IIV3, containing A/Perth/16/2009-like A(H3N2)] and 209 HCP who declined vaccination. Estimates of the percentage with high titers (≥40 and>100) and geometric mean fold change ratios (GMRs) to A/Perth/16/2009-like virus by number of prior vaccinations were adjusted for age, sex, race, education, household size, hospital care responsibilities, and study site. RESULTS: Post-vaccination GMRs were inversely associated with the number of prior vaccinations, increasing from 2.3 among those with 4 prior vaccinations to 6.2 among HCP with zero prior vaccinations (F[4,567]=9.97, p<.0005). Thirty-two percent of HCP with 1 prior vaccination achieved titers >100 compared to only 11% of HCP with 4 prior vaccinations (adjusted odds ratio=6.8, 95% CI=3.1 - 15.3). CONCLUSION: Our findings point to an exposure-response association between repeated IIV3 vaccination and HI for A(H3N2) and are consistent with recent VE observations. Ultimately, better vaccines and vaccine strategies may be needed in order to optimize immunogenicity and VE for HCP and other repeated vaccinees. |
Comparison of serum hemagglutinin and neuraminidase inhibition antibodies after 2010-2011 trivalent inactivated influenza vaccination in healthcare personnel
Laguio-Vila MR , Thompson MG , Reynolds S , Spencer SM , Gaglani M , Naleway A , Ball S , Bozeman S , Baker S , Martinez-Sobrido L , Levine M , Katz J , Fry AM , Treanor JJ . Open Forum Infect Dis 2015 2 (1) ofu115 BACKGROUND: Most inactivated influenza vaccines contain purified and standardized hemagglutinin (HA) and residual neuraminidase (NA) antigens. Vaccine-associated HA antibody responses (hemagglutination inhibition [HAI]) are well described, but less is known about the immune response to the NA. METHODS: Serum of 1349 healthcare personnel (HCP) electing or declining the 2010-2011 trivalent-inactivated influenza vaccine ([IIV3], containing A/California/7/2009 p(H1N1), A/Perth/16/2009 [H3N2], B/Brisbane/60/2008 strains) were tested for NA-inhibiting (NAI) antibody by a modified lectin-based assay using pseudotyped N1 and N2 influenza A viruses with an irrelevant (H5) HA. Neuraminidase-inhibiting and HAI antibody titers were evaluated approximately 30 days after vaccination and end-of-season for those with polymerase chain reaction (PCR)-confirmed influenza infection. RESULTS: In 916 HCP (68%) receiving IIV3, a 2-fold increase in N1 and N2 NAI antibody occurred in 63.7% and 47.3%, respectively. Smaller responses occurred in HCP age >50 years and those without prior 2009-2010 IIV3 nor monovalent A(H1N1)pdm09 influenza vaccinations. Forty-four PCR-confirmed influenza infections were observed, primarily affecting those with lower pre-exposure HAI and NAI antibodies. Higher pre-NAI titers correlated with shorter duration of illness for A(H1N1)pdm09 virus infections. CONCLUSIONS: Trivalent-inactivated influenza vaccine is modestly immunogenic for N1 and N2 antigens in HCP. Vaccines eliciting robust NA immune responses may improve efficacy and reduce influenza-associated morbidity. |
Results of a pilot study using self-collected mid-turbinate nasal swabs for detection of influenza virus infection among pregnant women
Thompson MG , Ferber JR , Odouli R , David D , Shifflett P , Meece JK , Naleway AL , Bozeman S , Spencer SM , Fry AM , Li K . Influenza Other Respir Viruses 2015 9 (3) 155-60 BACKGROUND: We evaluated the feasibility of asking pregnant women to self-collect and ship respiratory specimens. METHODS: In a preliminary laboratory study, we compared the RT-PCR cycle threshold (CT) values of influenza A and B viruses incubated at 4 storage temperatures (from 4-35 degrees C) for 6 time periods (8, 24, 48, 72, and 168 hours and 30-days), resulting in 24 conditions that were compared to an aliquot tested after standard freezing (-20 degrees C) (baseline condition). In a subsequent pilot study, during January-February, 2014, we delivered respiratory specimen collection kits to 53 pregnant women with a medically attended acute respiratory illness using three delivery methods. RESULTS: CT values were stable after storage at temperatures <27 degrees C for up to 72 hours for influenza A viruses and 48 hours for influenza B viruses. Of 53 women who received kits during the pilot, 89% collected and shipped nasal swabs as requested. However, 30% (14/47) of the women took over 2 days to collect and ship their specimen. The human control gene, ribonuclease P (RNase P), was detected in 100% of nasal swab specimens. However, the mean CT values for RNase P (26.5, 95% confidence interval [CI] = 26.0-27.1) and for the 8 influenza A virus positives in our pilot (32.2, 95% CI = 28.9-35.5) were significantly higher than the CTs observed in our 2010-12 study using staff-collected nasal pharyngeal swabs (p-values < .01). DISCUSSION: Self-collection of respiratory specimens is a promising research method, but further research is needed to quantify the sensitivity and specificity of the approach. |
Daily rifapentine for treatment of pulmonary tuberculosis. A randomized, dose-ranging trial
Dorman SE , Savic RM , Goldberg S , Stout JE , Schluger N , Muzanyi G , Johnson JL , Nahid P , Hecker EJ , Heilig CM , Bozeman L , Feng PJ , Moro RN , MacKenzie W , Dooley KE , Nuermberger EL , Vernon A , Weiner M . Am J Respir Crit Care Med 2015 191 (3) 333-43 RATIONALE: Rifapentine has potent activity in mouse models of tuberculosis chemotherapy but its optimal dose and exposure in humans are unknown. OBJECTIVES: We conducted a randomized, partially blinded dose-ranging study to determine tolerability, safety, and antimicrobial activity of daily rifapentine for pulmonary tuberculosis treatment. METHODS: Adults with sputum smear-positive pulmonary tuberculosis were assigned rifapentine 10, 15, or 20 mg/kg or rifampin 10 mg/kg daily for 8 weeks (intensive phase), with isoniazid, pyrazinamide, and ethambutol. The primary tolerability end point was treatment discontinuation. The primary efficacy end point was negative sputum cultures at completion of intensive phase. MEASUREMENTS AND MAIN RESULTS: A total of 334 participants were enrolled. At completion of intensive phase, cultures on solid media were negative in 81.3% of participants in the rifampin group versus 92.5% (P = 0.097), 89.4% (P = 0.29), and 94.7% (P = 0.049) in the rifapentine 10, 15, and 20 mg/kg groups. Liquid cultures were negative in 56.3% (rifampin group) versus 74.6% (P = 0.042), 69.7% (P = 0.16), and 82.5% (P = 0.004), respectively. Compared with the rifampin group, the proportion negative at the end of intensive phase was higher among rifapentine recipients who had high rifapentine areas under the concentration-time curve. Percentages of participants discontinuing assigned treatment for reasons other than microbiologic ineligibility were similar across groups (rifampin, 8.2%; rifapentine 10, 15, or 20 mg/kg, 3.4, 2.5, and 7.4%, respectively). CONCLUSIONS: Daily rifapentine was well-tolerated and safe. High rifapentine exposures were associated with high levels of sputum sterilization at completion of intensive phase. Further studies are warranted to determine if regimens that deliver high rifapentine exposures can shorten treatment duration to less than 6 months. Clinical trial registered with www.clinicaltrials.gov (NCT 00694629). |
Antibody response to influenza A(H1N1)pdm09 among healthcare personnel receiving trivalent inactivated vaccine: effect of prior monovalent inactivated vaccine
Gaglani M , Spencer S , Ball S , Song J , Naleway A , Henkle E , Bozeman S , Reynolds S , Sessions W , Hancock K , Thompson M . J Infect Dis 2014 209 (11) 1705-14 BACKGROUND: Few data are available on the immunogenicity of repeated annual doses of influenza A(H1N1)pdm09-containing vaccines. METHODS: We enrolled healthcare personnel (HCP) in direct patient care during the autumn of 2010 at 2 centers with voluntary immunization. We verified the receipt of A(H1N1)pdm09-containing monovalent inactivated influenza vaccine (MIIV) and 2010-2011 trivalent inactivated vaccine (TIV). We performed hemagglutination inhibition antibody (HI) assays on preseason, post-TIV, and end-of-season serum samples. We compared the proportion of HCPs with HI titer ≥ 40 against A(H1N1)pdm09 per receipt of prior-season MIIV, current-season TIV, both, or neither. RESULTS: At preseason (n = 1417), HI ≥ 40 was significantly higher among those who received MIIV (34%) vs those who did not (14%) (adjusted relative risk [ARR], 3.26; 95% confidence interval [CI], 2.72-3.81). At post-TIV (n = 865), HI ≥ 40 was lower among HCP who received MIIV and TIV (66%) than among those receiving only TIV (85%) (ARR, 0.93 [95% CI, .84-.997]). At end-of-season (n = 1254), HI ≥ 40 was 40% among those who received both MIIV and TIV and 67% among those receiving only TIV (ARR, 0.76 [95% CI, .65-.88]), 52% among those who received MIIV only, and 12% among those receiving neither. CONCLUSIONS: HCP immunization programs should consider effects of host immune response and vaccine antigenic distance on immunogenicity of repeated annual doses of influenza vaccines. |
Intermittent tuberculosis treatment for patients with isoniazid intolerance or drug resistance
Reves R , Heilig CM , Tapy JM , Bozeman L , Kyle RP , Hamilton CD , Bock N , Narita M , Wing D , Hershfield E , Goldberg SV . Int J Tuberc Lung Dis 2014 18 (5) 571-580 SETTING: Twenty tuberculosis (TB) clinics in the United States and Canada. OBJECTIVE: To evaluate the efficacy and safety of a 6- month intermittent regimen of rifampin (RMP), pyrazinamide (PZA) and ethambutol (EMB) in human immunodeficiency virus (HIV) negative patients with culture-confirmed pulmonary or extra-pulmonary tuberculosis and either isoniazid (INH) resistance or INH intolerance. DESIGN: Patients were enrolled in a single-arm clinical trial to receive intermittent dosing after at least 14 initial daily doses of RMP+PZA+EMB. Treatment was continued twice (BIW) or thrice weekly (TIW) per physician/patient preference for a total of 6 months, with 2 years of follow-up for relapse after treatment. RESULTS: From 1999 to 2004, 98 patients were enrolled, 78 with reported INH resistance and 20 with INH intolerance. BIW dosing was used in 77 and TIW in 21. Study treatment was completed in 73 (74%). Reasons for discontinuation were hepatic adverse events (n = 12), other adverse effects (n = 3) and other reasons (n = 10). Failure (n = 1) and relapse (n = 2) occurred in 3 (3.5%, 95%CI 1.2-9.8) of 86 patients eligible for efficacy analysis, all occurring in patients with cavitary, acid-fast bacilli smear-positive pulmonary TB. CONCLUSIONS: Intermittent RMP+PZA+EMB appears to be effective in HIV-negative patients, but the regimen is poorly tolerated, possibly due to the prolonged use of PZA. Alternative regimens of lower toxicity are needed. |
Barriers and facilitators to influenza vaccination and vaccine coverage in a cohort of health care personnel
Naleway AL , Henkle EM , Ball S , Bozeman S , Gaglani MJ , Kennedy ED , Thompson MG . Am J Infect Control 2014 42 (4) 371-5 BACKGROUND: Annual influenza vaccination is recommended for health care personnel (HCP). We describe influenza vaccination coverage among HCP during the 2010-2011 season and present reported facilitators of and barriers to vaccination. METHODS: We enrolled HCP 18 to 65 years of age, working full time, with direct patient contact. Participants completed an Internet-based survey at enrollment and the end of influenza season. In addition to self-reported data, we collected information about the 2010-2011 influenza vaccine from electronic employee health and medical records. RESULTS: Vaccination coverage was 77% (1,307/1,701). Factors associated with higher vaccination coverage include older age, being married or partnered, working as a physician or dentist, prior history of influenza vaccination, more years in patient care, and higher job satisfaction. Personal protection was reported as the most important reason for vaccination followed closely by convenience, protection of patients, and protection of family and friends. Concerns about perceived vaccine safety and effectiveness and low perceived susceptibility to influenza were the most commonly reported barriers to vaccination. About half of the unvaccinated HCP said they would have been vaccinated if required by their employer. CONCLUSION: Influenza vaccination in this cohort was relatively high but still fell short of the recommended target of 90% coverage for HCP. Addressing concerns about vaccine safety and effectiveness are possible areas for future education or intervention to improve coverage among HCP. |
What is the most reliable solid culture medium for tuberculosis treatment trials?
Joloba ML , Johnson JL , Feng PJ , Bozeman L , Goldberg SV , Morgan K , Gitta P , Boom HW , Heilig CM , Mayanja-Kizza H , Eisenach KD . Tuberculosis (Edinb) 2014 94 (3) 311-6 We conducted a prospective study to determine which solid medium is the most reliable overall and after two months of therapy to detect Mycobacterium tuberculosis complex (MTB). MTB isolation and contamination rates on LJ and Middlebrook 7H10 and 7H11 agar with and without selective antibiotics were examined in a single laboratory and compared against a constructed reference standard and MGIT 960 results. Of 50 smear positive adults with pulmonary TB enrolled, 45 successfully completed standard treatment. Two spot sputum specimens were collected before treatment and at week 8 and one spot specimen each at weeks 2, 4, 6, and 12. The MTB recovery rate among all solid media for pre-treatment specimens was similar. After 8 weeks, selective (S) 7H11 had the highest positivity rate. Latent class analysis was used to construct the primary reference standard. The 98.7% sensitivity of 7H11S (95% Wilson confidence interval 96.4%-99.6%) was highest among the 5 solid media (P = 0.003 by bootstrap); the 82.6% specificity of 7H10S (95% CI 75.7%-87.8%) was highest (P = 0.098). Our results support 7H11S as the medium of choice. Further studies in different areas where recovery and contamination are likely to vary, are recommended. |
How we determined the most reliable solid medium for studying treatment of tuberculosis
Heilig CM , Feng PJ , Joloba ML , Johnson JL , Morgan K , Gitta P , Boom WH , Mayanja-Kizza H , Eisenach KD , Bozeman L , Goldberg SV . Tuberculosis (Edinb) 2014 94 (3) 317-22 Phase 2 clinical trials for tuberculosis (TB) treatment require reliable culture methods to determine presence or absence of Mycobacterium tuberculosis (Mtb) over the course of therapy, as these trials are based primarily on bacteriological endpoints. We evaluate which of 5 solid media is most reliable: Lowenstein-Jensen (LJ) egg-base medium and 4 Middlebrook agar media (nonselective 7H10 and 7H11 and selective 7H10 and 7H11). We analyze 393 specimens from 50 HIV-negative Ugandan adults with newly-diagnosed, pulmonary TB and high acid-fast bacillus smear grade. Specimens were collected every 2-4 weeks during the first 12 weeks of therapy. We compare the results for each culture to 2 composite reference standards-one that was deemed positive if any solid culture was positive for Mtb and another based on latent-class analysis. Both reference standards established that the 2 selective Middlebrook media most reliably determine the presence or absence of Mtb (P < 0.003), largely because of their lower contamination rates. We also showed that results on Middlebrook media were similar to each other, while LJ was most frequently discordant. Contaminated results appeared more likely to be truly negative than to harbor undetected Mtb. |
Mycobacterium tuberculosis specific CD8(+) T cells rapidly decline with antituberculosis treatment
Nyendak MR , Park B , Null MD , Baseke J , Swarbrick G , Mayanja-Kizza H , Nsereko M , Johnson DF , Gitta P , Okwera A , Goldberg S , Bozeman L , Johnson JL , Boom WH , Lewinsohn DA , Lewinsohn DM . PLoS One 2013 8 (12) e81564 RATIONALE: Biomarkers associated with response to therapy in tuberculosis could have broad clinical utility. We postulated that the frequency of Mycobacterium tuberculosis (Mtb) specific CD8(+) T cells, by virtue of detecting intracellular infection, could be a surrogate marker of response to therapy and would decrease during effective antituberculosis treatment. OBJECTIVES: We sought to determine the relationship of Mtb specific CD4(+) T cells and CD8(+) T cells with duration of antituberculosis treatment. MATERIALS AND METHODS: We performed a prospective cohort study, enrolling between June 2008 and August 2010, of HIV-uninfected Ugandan adults (n = 50) with acid-fast bacillus smear-positive, culture confirmed pulmonary TB at the onset of antituberculosis treatment and the Mtb specific CD4(+) and CD8(+) T cell responses to ESAT-6 and CFP-10 were measured by IFN-gamma ELISPOT at enrollment, week 8 and 24. RESULTS: There was a significant difference in the Mtb specific CD8(+) T response, but not the CD4(+) T cell response, over 24 weeks of antituberculosis treatment (p<0.0001), with an early difference observed at 8 weeks of therapy (p = 0.023). At 24 weeks, the estimated Mtb specific CD8(+) T cell response decreased by 58%. In contrast, there was no significant difference in the Mtb specific CD4(+) T cell during the treatment. The Mtb specific CD4(+) T cell response, but not the CD8(+) response, was negatively impacted by the body mass index. CONCLUSIONS: Our data provide evidence that the Mtb specific CD8(+) T cell response declines with antituberculosis treatment and could be a surrogate marker of response to therapy. Additional research is needed to determine if the Mtb specific CD8(+) T cell response can detect early treatment failure, relapse, or to predict disease progression. |
Effectiveness of seasonal trivalent influenza vaccine for preventing influenza virus illness among pregnant women: a population-based case-control study during the 2010-2011 and 2011-2012 influenza seasons
Thompson MG , Li DK , Shifflett P , Sokolow LZ , Ferber JR , Kurosky S , Bozeman S , Reynolds SB , Odouli R , Henninger ML , Kauffman TL , Avalos LA , Ball S , Williams JL , Irving SA , Shay DK , Naleway AL . Clin Infect Dis 2013 58 (4) 449-57 BACKGROUND: Although vaccination with trivalent inactivated influenza vaccine (TIV) is recommended for all pregnant women, no vaccine effectiveness (VE) studies of TIV in pregnant women have assessed laboratory-confirmed influenza outcomes. METHODS: We conducted a case-control study over two influenza seasons (2010-2011 and 2011-2012) among Kaiser Permanente health plan members in two metropolitan areas in California and Oregon. We compared the proportion vaccinated among 100 influenza cases (confirmed by RT-PCR) with the proportions vaccinated among 192 controls with acute respiratory illness (ARI) who tested negative for influenza and 200 controls without ARI (matched by season, site, and trimester). RESULTS: Among influenza cases, 42% were vaccinated during the study season compared to 58% and 63% vaccinated among influenza-negative controls and matched ARI-negative controls, respectively. The adjusted VE (95% confidence interval [CI]) of the current season vaccine against influenza A and B was 44% (5%-67%) using the influenza-negative controls and 53% (24%-72%) using the ARI-negative controls. Receipt of the prior season's vaccine, however, had an effect similar to receipt of the current season's vaccine. As such, vaccination in either or both seasons had statistically similar adjusted VE using influenza-negative controls (VE point estimates range=51%-76%) and ARI-negative controls (48%-76%). CONCLUSIONS: Influenza vaccination reduced the risk of ARI associated with laboratory-confirmed influenza among pregnant women by over one-half, similar to VE observed among all adults during these seasons. |
Substitution of rifapentine for rifampin during intensive phase treatment of pulmonary tuberculosis: study 29 of the Tuberculosis Trials Consortium
Dorman SE , Goldberg S , Stout JE , Muzanyi G , Johnson JL , Weiner M , Bozeman L , Heilig CM , Feng PJ , Moro R , Narita M , Nahid P , Ray S , Bates E , Haile B , Nuermberger EL , Vernon A , Schluger NW . J Infect Dis 2012 206 (7) 1030-1040 BACKGROUND: Rifapentine administered 5 days per week has potent activity in mouse models of antituberculosis chemotherapy, but efficacy and safety data are limited in humans. We compared the antimicrobial activity and safety of rifapentine vs rifampin during the first 8 weeks of pulmonary tuberculosis treatment. METHODS: In total, 531 adults with sputum smear-positive pulmonary tuberculosis were randomized to rifapentine 10 mg/kg/dose or rifampin 10 mg/kg/dose, administered 5 days per week for 8 weeks (intensive phase), with isoniazid, pyrazinamide, and ethambutol. Coprimary outcomes were negative sputum culture on liquid and on solid media at completion of intensive phase. RESULTS: Negative cultures on solid media occurred in 145 of 174 participants (83.3%) in the rifampin group and 171 of 198 participants (86.4%) in the rifapentine group (difference, 3.0%; 95% confidence interval [CI]: - 4.3, 10.5); negative cultures in liquid media occurred in 110 of 169 (65.1%) in the rifampin group and 133 of 196 (67.9%) in the rifapentine group (difference, 2.8%; 95% CI: -6.9, 12.4). Among 529 participants who received study therapy, 40 of 254 participants (15.7%) in the rifampin group and 40 of 275 participants (14.5%) in the rifapentine group prematurely discontinued treatment (P = .79). CONCLUSIONS: The rifapentine regimen was safe but not significantly more active than a standard rifampin regimen, by the surrogate endpoint of culture status at completion of intensive phase. Assessment of higher exposures to rifapentine for tuberculosis treatment is warranted. Clinical Trials registration. NCT00694629. |
Reasons for non-participation in an international multicenter trial of a new drug for tuberculosis treatment
Lamunu D , Chapman KN , Nsubuga P , Muzanyi G , Mulumba Y , Mugerwa MA , Goldberg S , Bozeman L , Engle M , Saukkonen J , Mastranunzio S , Mayanja-Kizza H , Johnson JL . Int J Tuberc Lung Dis 2012 16 (4) 480-485 SETTING: Clinical trials can provide a high standard of patient care and contribute to scientific knowledge; however, only a fraction of the patients screened participate and receive treatment as part of a trial. OBJECTIVE: To explore reasons why patients were not enrolled in an international tuberculosis (TB) treatment trial and to compare experiences among study sites. DESIGN: An analysis of reasons why patients were not enrolled was conducted among patients screened for a TB clinical trial at 26 sites in North and South America, Africa, and Europe. RESULTS: Staff at study sites screened 1119 potential candidates for the trial: 61% (n = 686) were not enrolled due to 1) failure to meet eligibility criteria (n = 405, 59%), 2) site's decision (n = 168, 24%), or 3) candidate's choice (n = 113, 16%). Study staff recorded a total of 144 reasons for why they believed patients chose not to participate, including concerns over research (28%), conflicts with work or school (21%), and life-style and family issues (20%). Socio-demographic and geographic factors also influenced participation. CONCLUSION: Increased evaluation of screening outcomes and of specific interventions, such as improved education and communication about trial procedures, may increase the efficiency of screening and enrollment in clinical trials. (2012 The Union.) |
The expected emotional benefits of influenza vaccination strongly affect pre-season intentions and subsequent vaccination among healthcare personnel
Thompson MG , Gaglani MJ , Naleway A , Ball S , Henkle EM , Sokolow LZ , Brennan B , Zhou H , Foster L , Black C , Kennedy ED , Bozeman S , Grohskopf LA , Shay DK . Vaccine 2012 30 (24) 3557-65 BACKGROUND: The relative importance of different attitudes in predicting vaccination among healthcare personnel (HCP) is unclear. We hypothesized that HCP who feel at risk without vaccination or say they would regret not getting vaccinated would be more likely to get vaccinated than HCP who do not expect these emotional benefits. METHODS: A prospective cohort of 1544 HCP with direct patient care was enrolled from September 18 to December 18, 2010 at Scott & White Healthcare in Texas and Kaiser Permanente Northwest in Oregon and Washington. An Internet-based questionnaire assessed pre-season intention to be vaccinated and included 12 questions on attitudes about vaccination: single-item measures of perceived susceptibility and vaccine effectiveness, 5 items that were summed to form a concerns about vaccine scale, and 5 items summed to form an emotional benefits of vaccination scale. Influenza vaccination status for the 2010-2011 season and for 5 prior seasons was confirmed by medical record extraction. RESULTS: There were significant differences between vaccinated and unvaccinated HCP on all attitude items; 72% of vaccinated HCP agreed that they "worry less about getting the flu" if vaccinated, compared to only 26% of the unvaccinated (odds ratio=7.4, 95% confidence interval=5.8-9.5). In a multivariate model, the emotional benefits scale was the strongest predictor of 2010-2011 seasonal influenza vaccination, after adjusting for other attitude measures, prior vaccination history, and pre-season intention to be vaccinated. The predictive value of the emotional benefits scale was strongest for HCP with low pre-season intention to be vaccinated, where HCP vaccine receipt was 15% versus 83% for those with low versus high scores on the emotional benefits scale. CONCLUSIONS: The expected emotional benefits of vaccination strongly affect seasonal influenza vaccination among HCP, even after taking into account other attitudes, pre-season intentions, and prior vaccination history. These attitudes are promising targets for future vaccination campaigns. |
Active surveillance for influenza vaccine adverse events: the integrated vaccine surveillance system
Newes-Adeyi G , Greece J , Bozeman S , Walker DK , Lewis F , Gidudu J . Vaccine 2012 30 (6) 1050-5 OBJECTIVES: We conducted a pilot study of the Integrated Vaccine Surveillance System (IVSS), a novel active surveillance system for monitoring influenza vaccine adverse events that could be used in mass vaccination settings. METHODS: We recruited 605 adult vaccinees from a convenience sample of 12 influenza vaccine clinics conducted by public health departments of two U.S. metropolitan regions. Vaccinees provided daily reports on adverse reactions following immunization (AEFI) using an interactive voice response system (IVR) or the internet for 14 consecutive days following immunization. Followup with nonrespondents was conducted through computer-assisted telephone interviewing (CATI). Data on vaccinee reports were available real-time through a dedicated secure website. RESULTS: 90% (545) of vaccinees made at least one daily report and 49% (299) reported consecutively for the full 14-day period. 58% (315) used internet, 20% (110) IVR, 6% (31) CATI, and 16% (89) used a combination for daily reports. Of the 545 reporters, 339 (62%) reported one or more AEFI, for a total of 594 AEFIs reported. The majority (505 or 85%) of these AEFIs were mild symptoms. CONCLUSIONS: It is feasible to develop a system to obtain real-time data on vaccine adverse events. Vaccinees are willing to provide daily reports for a considerable time post vaccination. Offering multiple modes of reporting encourages high response rates. Study findings on AEFIs showed that the IVSS was able to exhibit the emerging safety profile of the 2008 seasonal influenza vaccine. |
Geographic differences in time to culture conversion in liquid media: tuberculosis trials consortium study 28. Culture conversion is delayed in Africa
Mac Kenzie WR , Heilig CM , Bozeman L , Johnson JL , Muzanye G , Dunbar D , Jost KC Jr , Diem L , Metchock B , Eisenach K , Dorman S , Goldberg S . PLoS One 2011 6 (4) e18358 BACKGROUND: Tuberculosis Trials Consortium Study 28, was a double blind, randomized, placebo-controlled, phase 2 clinical trial examining smear positive pulmonary Mycobacterium tuberculosis. Over the course of intensive phase therapy, patients from African sites had substantially delayed and lower rates of culture conversion to negative in liquid media compared to non-African patients. We explored potential explanations of this finding. METHODS: In TBTC Study 28, protocol-correct patients (n = 328) provided spot sputum specimens for M. tuberculosis culture in liquid media, at baseline and weeks 2, 4, 6 and 8 of study therapy. We compared sputum culture conversion for African and non-African patients stratified by four baseline measures of disease severity: AFB smear quantification, extent of disease on chest radiograph, cavity size and the number of days to detection of M. tuberculosis in liquid media using the Kaplan-Meier product-limit method. We evaluated specimen processing and culture procedures used at 29 study laboratories serving 27 sites. RESULTS: African TB patients had more extensive disease at enrollment than non-African patients. However, African patients with the least disease by the 4 measures of disease severity had conversion rates on liquid media that were substantially lower than conversion rates in non-African patients with the greatest extent of disease. HIV infection, smoking and diabetes did not explain delayed conversion in Africa. Some inter-site variation in laboratory processing and culture procedures within accepted practice for clinical diagnostic laboratories was found. CONCLUSIONS: Compared with patients from non-African sites, African patients being treated for TB had delayed sputum culture conversion and lower sputum conversion rates in liquid media that were not explained by baseline severity of disease, HIV status, age, smoking, diabetes or race. Further investigation is warranted into whether modest variation in laboratory processes substantially influences the efficacy outcomes of phase 2 TB treatment trials or if other factors (e.g., nutrition, host response) are involved. TRIAL REGISTRATION: ClinicalTrials.gov NCT00144417. |
6-month versus 36-month isoniazid preventive treatment for tuberculosis in adults with HIV infection in Botswana: a randomised, double-blind, placebo-controlled trial
Samandari T , Agizew TB , Nyirenda S , Tedla Z , Sibanda T , Shang N , Mosimaneotsile B , Motsamai OI , Bozeman L , Davis MK , Talbot EA , Moeti TL , Moffat HJ , Kilmarx PH , Castro KG , Wells CD . Lancet 2011 377 (9777) 1588-98 BACKGROUND: In accordance with WHO guidelines, people with HIV infection in Botswana receive daily isoniazid preventive therapy against tuberculosis without obtaining a tuberculin skin test, but duration of prophylaxis is restricted to 6 months. We aimed to assess effectiveness of extended isoniazid therapy. METHODS: In our randomised, double-blind, placebo-controlled trial we enrolled adults infected with HIV aged 18 years or older at government HIV-care clinics in Botswana. Exclusion criteria included current illness such as cough and an abnormal chest radiograph without antecedent tuberculosis or pneumonia. Eligible individuals were randomly allocated (1:1) to receive 6 months' open-label isoniazid followed by 30 months' masked placebo (control group) or 6 months' open-label isoniazid followed by 30 months' masked isoniazid (continued isoniazid group) on the basis of a computer-generated randomisation list with permuted blocks of ten at each clinic. Antiretroviral therapy was provided if participants had CD4-positive lymphocyte counts of fewer than 200 cells per muL. We used Cox regression analysis and the log-rank test to compare incident tuberculosis in the groups. Cox regression models were used to estimate the effect of antiretroviral therapy. The trial is registered at ClinicalTrials.gov, number NCT00164281. FINDINGS: Between Nov 26, 2004, and July 3, 2009, we recorded 34 (3.4%) cases of incident tuberculosis in 989 participants allocated to the control group and 20 (2.0%) in 1006 allocated to the continued isoniazid group (incidence 1.26% per year vs 0.72%; hazard ratio 0.57, 95% CI 0.33-0.99, p=0.047). Tuberculosis incidence in those individuals receiving placebo escalated approximately 200 days after completion of open-label isoniazid. Participants who were tuberculin skin test positive (ie, ≥5 mm induration) at enrolment received a substantial benefit from continued isoniazid treatment (0.26, 0.09-0.80, p=0.02), whereas participants who were tuberculin skin test-negative received no significant benefit (0.75, 0.38-1.46, p=0.40). By study completion, 946 (47%) of 1995 participants had initiated antiretroviral therapy. Tuberculosis incidence was reduced by 50% in those receiving 360 days of antiretroviral therapy compared with participants receiving no antiretroviral therapy (adjusted hazard ratio 0.50, 95% CI 0.26-0.97). Severe adverse events and death were much the same in the control and continued isoniazid groups. INTERPRETATION: In a tuberculosis-endemic setting, 36 months' isoniazid prophylaxis was more effective for prevention of tuberculosis than was 6-month prophylaxis in individuals with HIV infection, and chiefly benefited those who were tuberculin skin test positive. FUNDING: US Centers for Disease Control and Prevention and US Agency for International Development. |
The Pregnancy and Influenza Project: design of an observational case-cohort study to evaluate influenza burden and vaccine effectiveness among pregnant women and their infants
Thompson M , Williams J , Naleway A , Li DK , Chu S , Bozeman S , Hill HA , Cragan J , Shay DK . Am J Obstet Gynecol 2011 204 S69-76 The US Centers for Disease Control and Prevention is conducting an observational study of 300-500 women infected with influenza during pregnancy. Women are being recruited from members of the Kaiser Permanente health plan in 2 metropolitan areas before and during the 2010 through 2011 influenza season either following routine prenatal care visits or presentation with an acute respiratory infection. All enrolled mothers and their infants will be followed up through 1 month after delivery. Infants of mothers who had influenza during pregnancy and 1000 infants of mothers who were not diagnosed with influenza during pregnancy will be followed up for an additional 5 months. The Pregnancy and Influenza Project is focused on better understanding the burden of influenza during and after pregnancy and estimating the effectiveness of maternal influenza vaccination against influenza among women and their infants confirmed by real-time reverse transcription polymerase chain reaction assays. |
Organophosphorus and pyrethroid insecticide urinary metabolite concentrations in young children living in a southeastern United States city
Naeher LP , Tulve NS , Egeghy PP , Barr DB , Adetona O , Fortmann RC , Needham LL , Bozeman E , Hilliard A , Sheldon LS . Sci Total Environ 2010 408 (5) 1145-53 Pesticide metabolites are routinely measured in the urine of children in the United States. Although the sources of these metabolites are believed to include residues in food from agricultural applications and residues from applications in everyday environments (e.g., homes), few studies have been able to demonstrate an association between indoor residential pesticide applications and pesticide metabolite concentrations. To better quantify the effects of potential risk factors related to demographics, household characteristics, occupation, and pesticide use practices on urinary biomarker levels, we performed a study in a city (Jacksonville, Florida) previously determined to have elevated rates of pesticide use. We enrolled a convenience sample of 203 children ranging in age from 4 to 6 years; their caregivers completed a questionnaire and the children provided a urine sample, which was analyzed for a series of organophosphorus and pyrethroid insecticide metabolites. The questionnaire responses substantiated much higher pesticide use for the study participants as compared to other studies. Urinary metabolite concentrations were approximately an order of magnitude higher than concentrations reported for young children in other studies. Few statistically significant differences (at the p<0.05 level) were observed, however, several trends are worth noting. In general, mean urinary pesticide metabolite concentrations were higher for males, Caucasians, and those children living in homes with an indoor pesticide application occurring within the past four weeks. Comparing the urinary pesticide metabolite concentrations in this study to those reported in the NHANES and GerES studies showed that the children living in Jacksonville had substantially higher pyrethroid pesticide exposures than the general populations of the United States and Germany. Further research is needed in communities where routine pesticide use has been documented to obtain information on the most important routes and pathways of exposure and to develop the most effective strategies for reducing pesticide exposures for children. |
Substitution of moxifloxacin for isoniazid during intensive phase treatment of pulmonary tuberculosis
Dorman SE , Johnson JL , Goldberg S , Muzanye G , Padayatchi N , Bozeman L , Heilig CM , Bernardo J , Choudhri S , Grosset JH , Guy E , Guyadeen P , Leus MC , Maltas G , Menzies D , Nuermberger EL , Villarino M , Vernon A , Chaisson RE , Tuberculosis Trials Consortium . Am J Respir Crit Care Med 2009 180 (3) 273-80 RATIONALE: Moxifloxacin has potent activity against Mycobacterium tuberculosis in vitro and in a mouse model of antituberculosis (TB) chemotherapy, but data regarding its activity in humans are limited. OBJECTIVES: Our objective was to compare the antimicrobial activity and safety of moxifloxacin versus isoniazid during the first 8 weeks of combination therapy for pulmonary TB. METHODS: Adults with sputum smear-positive pulmonary TB were randomly assigned to receive either moxifloxacin 400 mg plus isoniazid placebo, or isoniazid 300 mg plus moxifloxacin placebo, administered 5 days/week for 8 weeks, in addition to rifampin, pyrazinamide, and ethambutol. All doses were directly observed. Sputum was collected for culture every 2 weeks. The primary outcome was negative sputum culture at completion of 8 weeks of treatment. MEASUREMENTS AND MAIN RESULTS: Of 433 participants enrolled, 328 were eligible for the primary efficacy analysis. Of these, 35 (11%) were HIV positive, 248 (76%) had cavitation on baseline chest radiograph, and 213 (65%) were enrolled at African sites. Negative cultures at Week 8 were observed in 90/164 (54.9%) participants in the isoniazid arm, and 99/164 (60.4%) in the moxifloxacin arm (P = 0.37). In multivariate analysis, cavitation and enrollment at an African site were associated with lower likelihood of Week-8 culture negativity. The proportion of participants who discontinued assigned treatment was 31/214 (14.5%) for the moxifloxacin group versus 22/205 (10.7%) for the isoniazid group (RR, 1.35; 95% CI, 0.81, 2.25). CONCLUSIONS: Substitution of moxifloxacin for isoniazid resulted in a small but statistically nonsignificant increase in Week-8 culture negativity. |
Relapse associated with active disease caused by Beijing strain of Mycobacterium tuberculosis
Burman WJ , Bliven EE , Cowan L , Bozeman L , Nahid P , Diem L , Vernon A , Tuberculosis Trials Consortium . Emerg Infect Dis 2009 15 (7) 1061-7 The role of microbial factors in outcomes of tuberculosis treatment has not been well studied. We performed a case-control study to evaluate the association between a Beijing strain and tuberculosis treatment outcomes. Isolates from patients with culture-positive treatment failure (n = 8) or relapse (n = 54) were compared with isolates from randomly selected controls (n = 296) by using spoligotyping. Patients with Beijing strains had a higher risk for relapse (odds ratio [OR] 2.0, 95% confidence interval [CI] 1.0-4.0, p = 0.04) but not for treatment failure. Adjustment for factors previously associated with relapse had little effect on the association between Beijing strains and relapse. Beijing strains were strongly associated with relapse among Asian-Pacific Islanders (OR 11, 95% CI 1.1-108, p = 0.04). Active disease caused by a Beijing strain was associated with increased risk for relapse, particularly among Asian-Pacific Islanders. |
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