TB NOTES

TB Education and Training Network Conference, September 2016

The TB Education and Training Network (TB ETN) and TB Program Evaluation Network Conference (TB PEN) will be held in Atlanta, Georgia, September 20-22, 2016.

Conference information will be available in late March on the TB ETN webpage.

Submitted by Peri Hopkins, MPH, DTBE

Recent TBTC Activities

The TB Trials Consortium has been active in the past year. Thanks to strong support from U.S. TB programs and from the Division and Center leadership, this group of domestic and international sites continues to pursue its aims to shorten and simplify TB prevention and control. The current group of sites are funded through 2019, and include clinical locations in the United States, Spain, Peru, Uganda, Kenya, South Africa, Vietnam, and Hong Kong. Recent and current activities include the following:

• TBTC Study 31 (ACTG A5349): This large (2500 patients) phase 3 trial is just beginning to enroll. It is being implemented as a collaboration between TBTC and the National Institute of Allergy and Infectious Diseases’ Adult AIDS Clinical Trials Group (ACTG). It aims to demonstrate the non-inferiority of 4-month regimen using high-dose daily rifapentine and moxifloxacin. The study will enroll at over 40 sites worldwide.  

• TBTC Study 32 (“Opti-Q”): This phase 2 study is about 50% enrolled. It is being implemented as a collaboration with Dr. R. Horsburgh and Boston University. It aims to determine the optimal dose of levofloxacin in the treatment of MDR TB, using pharmacokinetic and pharmacodynamic measures of efficacy.

• TBTC Study 33 (“iAdhere”): This phase 4 prevention trial has been completed, and a final report is in clearance. It compared adherence among three approaches to the use of the 12-dose latent TB infection (LTBI) 3HP regimen: DOT, SAT (self-administered therapy), and SAT enhanced by text messaging. Results were presented at the Conference on Retroviruses and Opportunistic Infections in 2015: self-administration resulted in modest declines in adherence, but it is likely that this will prove acceptable to many U.S. programs, since the LTBI treatment completion rate nationally has been hovering around 50% with the 9-month isoniazid regimen.

• TBTC Study 34 (ACTG A5295): This phase 3 diagnostic study assessed the performance of the Gene Xpert PCR diagnostic in the United States and internationally. It was implemented with ACTG leading, and TBTC assisting with enrollment in the U.S. The study has been completed, and published results appeared online with Clinical Infectious Diseases in February 2016.

• TBTC Study 35: This is a phase 2 study of the pharmacokinetics of rifapentine in infants and young children, using a newly-developed child-friendly water-dispersible mango-flavored formulation produced by Sanofi. The trial will be implemented in South Africa and is slated to begin enrollment in late 2016. If successful, the goal is international licensure of a child-friendly formulation for both pediatric contacts and pediatric TB cases.

• TBTC Study 36: This is an observational study of standard TB treatment, designed to run when other treatment trials are not in progress, in order to provide a platform for important sub-studies or specimen collection efforts. Study 36 has enrolled over 200 patients in the past year, as preparations for Study 31 were underway. It has provided specimens for half a dozen “platform studies,” and has provided biomarker specimens that will satisfy half of TBTC’s commitment to participate in an international biomarker banking activity led by the Gates-funded TB Alliance (see below).

• TBTC Study 36A: This study provides specimens from patients enrolled in Study 36 or in Study 31 to the TB Alliance Biomarker Bank effort, also known as Consortium for TB Biomarkers (CTB2).This bank, being created by the joint efforts of the TB Alliance, the TBTC, and the ACTG, will allow investigators world-wide to access critically needed TB patient specimens. These specimens will be used for the development of a TB treatment biomarker which could simplify and accelerate the pace of TB clinical trials. The specimen bank is administered by a steering committee which includes representatives from the three contributing groups.

TBTC clinical trials are all registered at ClinicalTrials.gov prior to beginning; more information on most trials can be found there or on the TBTC webpage.

The TBTC had its annual Divisional review at CDC (the “SAGE” meeting) on March 8, 2016.

On May 23-25, 2016 TBTC will hold its 35th semiannual meeting in Atlanta.Those interested to attend should contact Ms. Barbara DeCausey (404-639-5330; tbtcresearchadmin@cdc.gov).

Submitted by Barbara DeCausey, MPH, MBA, DTBE

The International Union against Tuberculosis and Lung Disease, North American Region, Honors Dr. Wanda Walton’s Contributions to TB Prevention, Diagnosis, and Care

The International Union against Tuberculosis and Lung Disease, North American Region recently honored Dr. Wanda Walton with the Lifetime Achievement Award in recognition of her outstanding commitment to TB prevention, control, and care during her career.

After earning her Masters of Education degree with a focus on Community Health, Dr. Walton began her career working for the DeKalb County Health Department in Atlanta, Georgia in 1979. Serving first as an Epidemiologist and then as a Senior Health Educator, Dr. Walton quickly learned the importance of education as a means to control and eliminate disease and went on to complete a Doctorate in Philosophy, majoring in Health Education/Health Promotion/Health Behavior, from the University of Alabama at Birmingham in 2003.

In 1989, Dr. Walton joined the U.S. Centers for Disease Control and Prevention’s (CDC) Division of Tuberculosis Control (now DTBE) as the first TB/HIV Health Education Specialist. Charged with the task of developing training materials for healthcare providers, Dr. Walton soon recognized the need to develop accurate and up-to-date materials for patients, their families, and communities, as well. In addition to developing and testing the Division’s first patient brochures, Dr. Walton proposed and led the development of the Self-Study Modules on Tuberculosis. Following nation-wide distribution through print-based modules, satellite-based educational sessions, and CDC’s first e-learning website, this 9-module series was lauded among TB programs in the United States and across the globe. The first edition of the Self-Study Modules were presented a Freddie Award, known as the “Oscar of Medicine,” in the category of Infectious Diseases at the 1999 International Health & Medical Film Competition, and were recognized for excellence in media, communication, and training design from the prestigious International Society for Improved Performance. The series has been so well received since its inception that TB programs worldwide continue to use, translate, and adapt the materials to train new staff. 

In the picture (left to right): Award Recipient Wanda Walton, PhD, MEd; Sundari Mase, MD, MPH

Dr. Walton continues to support, inspire, and mentor providers and educators in programs across North America and around the globe to enhance their capacities to produce and share relevant, high-quality TB education and training tools and resources. In direct response to the 1999 National Strategic Plan for TB Education and Training, Dr. Walton and her staff spearheaded the creation of the Tuberculosis Education and Training Network (TB ETN) in 2000 to bring TB professionals together to network, share resources, and build education and training skills. She also led the development of the Find TB Resources website, a one-stop site for TB education and training resources.

Dr. Walton’s steadfast belief in the importance of education as a means to eliminate TB has and continues to influence critical decisions on policy and funding related to TB education and training in the United States and internationally. Those who have had the pleasure to work alongside her cannot help but adopt for their own her oft repeated sentiment, “Efficient TB programs are not run by poorly trained or poorly educated staff.”

Submitted by Joan Mangan, PhD, DTBE

World TB Day 2016

This year, DTBE selected Unite to End TB  as the 2016 World TB Day theme.  In doing so, DTBE highlighted the significant progress that is being made toward ending TB every day, such as testing and treating high risk populations for latent TB infection, improving diagnostics and treatments, improving surveillance efforts, and educating health care providers to “Think TB.” 

DTBE remains committed to supporting the important work that is being done to eliminate TB in communities around the United States. The division launched a project to highlight stories of success in TB prevention and control. The CDC U.S. TB Elimination Champions provided an opportunity to recognize accomplishments and learn best practices from organizations and people who are making a significant contribution toward ending TB in their community. Success stories were posted on the CDC U.S. TB Elimination Champions page during the week of World TB Day. Learn more about those who are working toward TB elimination.

Submitted by Dana Tumblin, MMC, DTBE

The Program Evaluation Team Joins the Data Management and Statistics Branch

Program Evaluation is a vital component of TB program activities. The Field Services Branch (FSB) (proposed) within DTBE has included a Program Evaluation Team for a number of years. The primary goals of the Team were to ensure implementation of the key provisions of program evaluation outlined in the cooperative agreement CDC has with external state and local programs; to provide transparent and easily understood program evaluation information to TB control programs that would serve them in meeting TB national goals and objectives; to galvanize TB control programs to implement and use the National TB Indicators Project (NTIP) to prioritize program areas for improvement; and to foster greater accountability for performance in TB control and activities.

In 2015, the Program Evaluation Team was augmented with health economics expertise, renamed the Program Evaluation and Health Economics Team, and moved to the Data Management, Statistics, and Evaluation Branch (DMSEB) (proposed). The integration of these two functions will provide a broader level of support and expertise that will continue to focus on critical evaluation functions while providing additional expertise to internal and external partners.

In conjunction with this change, Maureen Kolasa, RN, MPH will serve as the Team Lead for the Program Evaluation and Health Economics Team and will be the primary DTBE point of contact for program evaluation activities beginning March 21, 2016. Ms.  Kolasa can be reached via email at mxk2@cdc.gov.

Submitted by David Wilson, MEd, DTBE

Laboratory Leadership Service Fellow Joins DTBE’s Laboratory Branch

Sheila Akinyi Okoth, Ph.D., joined DTBE’s Laboratory Branch (LB) in July 2015 as an inaugural member of the Laboratory Leadership Service (LLS) fellowship class. The LLS is a 2-year laboratory fellowship that provides early career laboratory scientists with high-quality training that focuses on biosafety, quality management systems, and management and leadership competencies and includes a unique curriculum, core activities for learning, and mentorship to focus on the requirements of public health laboratories. Sheila is assigned to the Reference Laboratory Team (RLT), a Clinical Laboratory Improvement Amendments (CLIA)-regulated laboratory where she is being mentored by Dr. Beverly Metchock, RLT Team Lead, and Lois Diem, LB Quality Management Officer.

Sheila is working alongside Lois Diem to continue implementation of Quality Management Systems (QMS) including biosafety across LB research, clinical service, and technical consultation activities. The LB is one of five laboratories participating in a pilot project coordinated by the Office of the Associate Director of Laboratory Science and Safety with the purpose of attaining accreditation to ISO 17025.

Sheila is also working with the LB Laboratory Capacity Team, the Communications Team within the Communications, Education, and Behavioral Studies Branch, and the Association of Public Health Laboratories to develop an educational module that covers molecular diagnostics for TB drug resistance for a non-technical audience. The purpose of this module is to provide individuals involved in patient management and public health with an overview of mutations associated with TB drug resistance, molecular tests used to detect these mutations, and information to assist with interpretation of molecular testing results.

Other projects in which Sheila is involved include conducting Biological Risk Assessments and participating in CDC-wide workgroups such as the Next Generation Sequencing Quality Workgroup and the CDC Laboratory Biosafety Training Project. 

Prior to joining LB, Sheila worked as a post-doctoral fellow in the Malaria Branch of the Division of Parasitic Diseases and Malaria at the Centers for Disease Control and Prevention.  She received her B.S. in Biology from the State University of New York, College of Cortland and her Ph.D. in Immunology and Molecular Pathogenesis from Emory University. She anticipates that upon completion of the LLS fellowship, she will be well trained in the highest standards of safety and quality management. 

Submitted by Sheila Akinyi Okoth, PhD, DTBE

An Updated Strategic Direction for TB Surveillance

Dr. Adam Langer has recently joined the Surveillance, Epidemiology, and Outbreak Investigations Branch as the Surveillance Team Lead. Moving into 2016 with a new Team Lead, the Surveillance Team had the opportunity to develop a formal strategic plan to align with the National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention (NCHHSTP) and DTBE Strategic Plans.

The Surveillance Team’s Strategic Plan has a 5-year horizon, with three goals to be achieved from 2016-2020:

• To revise the Report of Verified Case of TB (RVCT) to better capture U.S. TB epidemiology data;
• To promote increased and innovative use of surveillance data to better understand evolving TB epidemiology; and
• To implement national surveillance for LTBI.

Several objectives have been identified in support of the plan’s 3 goals:

• To establish an RVCT revision workgroup;
• To identify data elements to add, revise, or remove from the RVCT;
• To improve availability of national surveillance data;
• To increase epidemiologic analyses of surveillance data;
• To increase use of surveillance data for program improvement;
• To support new clinic-based online LTBI reporting system “Surveillance for TB Elimination Management System” (STEMS);
• To assess existing external LTBI surveillance data sources (e.g., state-based systems); and
• To initiate development of National LTBI Surveillance System infrastructure.

Reported by Adam Langer, DVM, MPH, DACVPM, DTBE

Tuberculosis Indicator Data

Through the CDC’s regulatory authority, panel physicians around the world screen U.S.-bound immigrants and refugees for inadmissible (Class A) health conditions such as active TB disease. Panel physicians are required to maintain TB Indicator data which includes data specific to any TB disease diagnosis, including laboratory results and treatment outcomes.

TB Indicator data allow CDC to monitor the effectiveness and impact of the U.S. overseas TB screening program. CDC’s Tuberculosis Technical Instructions require that data be submitted by all panel sites annually. As with all data, there are many inherent limitations, including failure by panel sites to report data, incomplete submissions, and inconsistent quality in reporting.

2014 TB Indicator Data – Summary of Key Results:

Reported from 146 (96%) countries with a U.S. panel physician program and 304 (87%) U.S. panel sites (% of total U.S. screening countries or sites, respectively):

• Total of 631,100 applicants screened; 3.9% with chest radiographs suggestive of TB
• Total of 1,450 applicants diagnosed with Class A TB disease (230 per 100,000 screened)
• Of all 1,135 culture-positive TB cases, 802 (71%) were smear-negative
• Of all TB cases, 276 were resistant to at least one drug (19%), 44 had MDR-TB (3%), and one case had XDR-TB (0.07%)

CDC’s Tuberculosis Technical Instructions require that immigrants and refugees with active TB disease be completely treated and culture-negative prior to U.S. entry. 

CDC is working diligently with panel sites in pursuit of quality reporting of TB Indicator data to assist panel physicians in improving their screening, thereby decreasing the number of immigrants and refugees entering the U.S. with active TB disease.

Submitted by Tracy Dowdell, MBA, Division of Global Migration and Quarantine

Baker BJ, Winston CA, Liu Y, France AM, Cain KP. Abrupt decline in tuberculosis among foreign-born persons in the United States. PLoS One. 2016 Feb 10;11(2):e0147353. doi: 10.1371/journal.pone.0147353. eCollection 2016. PMID: 26863004

Burmen B, Modi S, Cavanaugh JS, Muttai H, McCarthy KD, Alexander H, Cain K. Tuberculosis screening outcomes for newly diagnosed persons living with HIV, Nyanza Province, Kenya, 2009. Int J Tuberc Lung Dis. 2016 Jan;20(1):79-84. doi: 10.5588/ijtld.15.0053. PMID: 26688532

CDC (Buss BF, Keyser-Metobo A, Rother J, Holtz, L, Gall K, Jereb J, Murphy CN, Iwen PC, Robbe-Austerman S, Holcomb, MA, Infield P) Possible airborne person-to-person transmission of mycobacterium bovis — Nebraska 2014–2015. MMWR 2016 March 4; 65(8):197–201.

CDC (Ratto J, Ivy III W, Purfield A, Bangura J, Omoko A, Boateng I, Duffy N, Sims G, Beamer B, Pi-Sunyer T, Kamara S, Conteh S, Redd J) Notes from the field: Ebola virus disease response activities during a mass displacement event after flooding — Freetown, Sierra Leone, September–November, 2015. MMWR 2016 Feb 26;65(7):188–9.

CDC (Young KH, Ehman M, Reves R, Peterson Maddox BL, Khan A, Chorba TL, Jereb J) Tuberculosis contact investigations—United States, 2003–2012. MMWR 2016 Jan 1;64:1369-74.

Chorba T, Breedlove B. Depictions of heroism in battle and anguish from tuberculosis. Emerg Infect Dis. 2016 Mar;22(3). doi: 10.3201/eid2203.AC2203.

Dave PV, Shah AN, Nimavat PB, Modi BB, Pujara KR, Patel P, Mehariya K, Rade KV, Shekar S, Sachdeva KS, Oeltmann JE, Kumar AM. Direct observation of treatment provided by a family member as compared to non-Family member among children with new tuberculosis: A pragmatic, non-Inferiority, cluster-randomized trial in Gujarat, India. PLoS One. 2016 Feb 5;11(2):e0148488. doi: 10.1371/journal.pone.0148488. eCollection 2016. PMID: 26849442

Furin J, Alirol E, Allen E, Fielding K, Merle C, Abubakar I, Andersen J, Davies G, Dheda K, Diacon A, Dooley KE, Dravnice G, Eisenach K, Everitt D, Ferstenberg D, Goolam-Mahomed A, Grobusch MP, Gupta R, Harausz E, Harrington M, Horsburgh CR, Lienhardt C, McNeeley D, Mitnick CD, Nachman S, Nahid P, Nunn AJ, Phillips P, Rodriguez C, Shah S, Wells C, Thomas-Nyang’wa B, du Cros P. Drug-resistant tuberculosis clinical trials: Proposed core research definitions in adults. Int j tuberc Lung Dis. 2016 Mar 20(3): 290-5. doi: http://dx.doi.org/10.5588/ijtld.15.0490.

Heidebrecht CL, Podewils LJ, Pym AS, Cohen T, Mthiyane T, Wilson D. Assessing the utility of Xpert(®) MTB/RIF as a screening tool for patients admitted to medical wards in South Africa. Sci Rep. 2016 Jan 20;6:19391. doi: 10.1038/srep19391. PMID: 26786396.

Jewett A, Bell T, Cohen NJ, Buckley K, Leino EV, Even S, Beavers S, Brown C, Marano N. US college and university student health screening requirements for tuberculosis and vaccine-preventable diseases, 2012. J Am Coll Health. 2016 Jan 5:0. [Epub ahead of print]. PMID: 26730492.

Juarez-Reyes M, Gallivan M, Chyorny A, O’Keeffe L, Shah NS. Completion rate and side-effect profile of three-month isoniazid and rifapentine treatment for latent tuberculosis infection in an urban county jail. Open Forum Infect Dis. 2016 Jan 6;3(1):ofv220. doi: 10.1093/ofid/ofv220. eCollection 2016 Jan. PMID: 26885547.

Kim L, Moonan PK, Heilig CM, Woodruff RS, Kammerer JS, Haddad MB. Factors associated with recurrent tuberculosis more than 12 months after treatment completion. Int J Tuberc Lung Dis. 2016 Jan;20(1):49-56. doi: 10.5588/ijtld.15.0442. PMID: 26688528.

Luetkemeyer AF, Firnhaber C, Kendall MA, Wu X, Mazurek GH, Benator DA; Arduino R, Fernandez M, Guy E, Johnson P, Metchock B, Sattler F, Telzak E, Wang YF, Weiner M, Swindells S, Sanne IM, Havlir DV, Grinsztejn B, Alland D; AIDS Clinical Trials Group A5295 and Tuberculosis Trials Consortium Study 34 Teams. Evaluation of Xpert MTB/RIF to identify pulmonary tuberculosis in tuberculosis suspects from low and higher prevalence settings compared to acid fast smear and culture. Clin Infect Dis. 2016 Feb 2. pii: ciw035. [Epub ahead of print] PMID: 26839383.

Nnadi CD, Anderson LF, Armstrong LR, Stagg HR, Pedrazzoli D, Pratt R, Heilig CM, Abubakar I, Moonan PK. Mind the gap: TB trends in the USA and the UK, 2000-2011. Thorax. 2016 Feb 23. pii: thoraxjnl-2015-207915. doi: 10.1136/thoraxjnl-2015-207915. [Epub ahead of print]. PMID: 26907187.

Roland KB, Benard VB, Greek A, Hawkins NA, Lin L. Changes in knowledge and beliefs about human papillomavirus and cervical cancer screening intervals in low-income women after an educational intervention. J Prim Care Community Health. 2016 Jan 13. pii: 2150131915624869. [Epub ahead of print] PMID: 26763304 PMID: 26763304.

Sharma A, Bloss E, Heilig CM, Click ES. Tuberculosis caused by mycobacterium africanum, United States, 2004-2013. Emerg Infect Dis. 2016 Mar;22(3):396-403. doi: 10.3201/eid2203.151505.  PMID: 26886258.

Tupasi T, Garfin AM, Kurbatova EV, Mangan JM, Orillaza-Chi R, Naval LC, Balane GI, Basilio R, Golubkov A, Joson ES, Lew WJ, Lofranco V, Mantala M, Pancho S, Sarol JN Jr. Factors associated with loss to follow-up during treatment for multidrug-resistant tuberculosis, the Philippines, 2012-2014. Emerg Infect Dis. 2016 Mar;22(3). doi: 10.3201/eid2203.151788. PMID: 26889786. 

Velásquez GE, Cegielski JP, Murray MB, Yagui MJ, Asencios LL, Bayona JN, Bonilla CA, Jave HO, Yale G, Suárez CZ, Sanchez E, Rojas C, Atwood SS, Contreras CC, Cruz JS, Shin SS. Impact of HIV on mortality among patients treated for tuberculosis in Lima, Peru: A prospective cohort study. BMC Infect Dis. 2016 Feb 1;16(1):45. doi: 10.1186/s12879-016-1375-8. PMID: 26831140.