December 2016 Newsletter

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Department of Medicine eNewsletter
December 2016
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department interview
Henry Boom, MD, Interim Division Chief of Infectious Diseases and HIV Medicine, discusses the evolution of tuberculosis health care, highlights factors affecting the spread of disease currently and shares the latest updates on the study examining a small population resistant to the infection.
Tuberculosis was a problem in the United States in the 1940s and 1950s and resurfaced again in the 1980s. Why does the issue still remain unresolved and what is the importance of it globally?

Currently tuberculosis (TB) is not a serious public health problem in the United States; the disease is well-controlled through screening, prompt diagnosis and treatment, and other public health measures. Nationally TB rates continue to decline; in fact, the CDC is talking about the elimination of TB in the U.S.

However, the TB paradox is that many people can become infected with Mycobacterium tuberculosis (Mtb), its causative agent, and carry Mtb as latent bacteria in their body for many years, and remain asymptomatic. Only a small percentage of people (5 - 10 percent) go on to develop the TB disease. Roughly speaking, approximately one third of the world's population is thought to carry latent Mtb, which results in a sizeable disease burden globally even if only 5 - 10 percent progress to TB. The United States is a country of visitors and immigrants; people come from all over the world, including places where TB is prevalent, such as Africa and Asia. Therefore, TB cases in the United States are increasingly found in persons who come from TB endemic countries. TB disproportionally affects socially disadvantaged groups who suffer from poor nutrition, crowded living conditions and poor access to health services, delaying diagnosis and treatment and therefore increasing the risk of spreading the infection and disease.

How has the disease been evolving over the past few years? Are there new contributing factors? What are the characteristics of the populations we should pay close attention to now?

In many parts of the world, we are building mega-cities, where people are crowded together and slums continue to expand. These crowded urban environments in Asia, Africa and South America contribute to the risk for spreading and developing TB. In addition, HIV and diabetes increase the risk of TB. Increasing drug resistance is compounding the problem. Luckily in most cases, TB is drug-sensitive and effective treatments are available. The main concern is to ensure patients get a timely diagnosis and access to health care for the full six months of drug treatment. The main public health focus to control the disease is identifying TB early and ensuring care is provided to those affected.

What is the treatment for multi-drug resistant TB? How is it being controlled now?

Multi-drug resistant TB (MDR-TB) has similar causes as drug-resistant bacteria in general, which include suboptimal treatment, poor drug access or incomplete course of treatment due to noncompliance or structural health care service delivery issues. Though some times MDR-TB can be caused by a patient who fails to finish drug treatment, often the responsibility lies with physicians who prescribe an inappropriate regimen or the public health system that does not have an adequate supply of medications or renders health care difficult.

Though the drugs are expensive and toxic, there is treatment for MDR-TB, and when treatment is done correctly, patients can be cured. There is a lot of new expertise being developed around the world for treating MDR-TB, and people are working hard on regimens that are more effective than those we currently have. Over the past few years, we had two promising drugs, delamanid and bedaquiline, introduced for MDR-TB treatment, that are able to clear the bacteria more quickly. There are now studies taking place to determine if these new drugs are also effective and safe for drug-sensitive TB.

How is TB research currently evolving?

Current TB research is focused on four areas: vaccine development, pathogenesis research, diagnostics, and development of new drug regimens with new drugs or re-purposing of old drugs. We have made the most progress in molecular diagnostics, where measurement of Mtb-DNA is allowing for more accurate and easier diagnosis. We are also identifying the causes and mechanisms that on the one hand increase the risk for progression to TB and on the other allow some to resist developing disease and even resist Mtb infection.

You were recently awarded grants from NIH and the Bill & Melinda Gates Foundation to study the phenomenon of HIV- and HIV+ persons who do not develop Mtb infection despite prolonged exposure to the bacteria. How can following these individuals help us in the future? What is the significance of the study?

We were some of the first researchers to describe a group of HIV- and HIV+ people in Uganda who despite heavy exposure to Mtb never seem to develop evidence for Mtb infection and thus appear to be resistant. We discovered this group when studying TB households, analyzing the progression from Mtb exposure to infection and development of disease among household members. We noticed that a small group, about 5-10 percent, were resistant to Mtb infection as defined by the absence of a tuberculin skin test (TST) for two years upon repeat testing, which we call Mtb "resisters." Clinically, a positive TST in an otherwise healthy person is used to define Mtb infection. As we are trying to develop new ways to prevent and treat TB, we look at this population of resisters, hoping to understand the mechanisms they use to control Mtb in their lungs. If we can successfully understand this resistance process and the immune mechanisms used, we can use it to develop a new vaccine, and identify a biomarker that allows stratifying persons at high risk for developing Mtb disease - i.e., TB. In order to do that effectively, we need to analyze the immune system in detail and study T cells, B cells, macrophages and antibodies to identify genes and molecules that contribute to resistance of the infection.

We believe that the key to this resistance phenomenon occurs at the level of the immune system. Currently we are following two populations of resisters, one among miners in South Africa, who have the highest rates of TB in the world, and the other household contacts in Uganda. The hope is that this will help us define the mechanisms more precisely. If there is a universal immune mechanism, it should be detectable in both groups.

What is the importance of the recently obtained training grant for biomedical research between Case Western Reserve University and Uganda? How have the health care and patient outcomes changed over the years of this partnership and collaboration? What changes do you hope to witness following this research project?

The clinical research and training collaboration between Uganda, Case Western Reserve University, and the Division of Infectious Diseases & HIV Medicine has been long-standing, spanning more than 25 years. HIV was the main focus of our work in Uganda initially; however, since TB is the most common manifestation and complication of HIV infection, the focus on TB became an early and natural progression of the Uganda-CWRU Research Collaboration (UCRC). UCRC's activities have resulted in improving public health as well as clinical and research training in HIV and TB for Ugandan faculty and students. Through our studies we have had a significant impact on TB and HIV-TB care, improving patient treatment, optimizing drug choices and minimizing the use of toxic drugs and subsequent side effects. Our collaboration has since matured and the evolution of training has advanced from educating physicians and nurses in public health and clinical research to building the groundwork for basic biomedical research. Though there has been significant progress in health care and research that is now led by Ugandan staff, technicians and faculty, health services in Uganda continue to be variable. Our goal is to continue to set a good example, provide the necessary training and boost TB and HIV-TB research in Uganda to contribute to the control and treatment of these two epidemics.

department news report
Division of General Internal Medicine

Clifford Packer, MD,
published a book titled "Writing Case Reports: A Practical Guide from Conception through Publication." The book provides physicians and medical students with a practical, step-by-step guide on how to write and publish a medical case report.




Division of Hematology & Oncology
Clark Distelhorst, MD, received a $200,000 award from the Harrington Scholar-Innovator Program to support his work on the development of a novel Bcl-2 inhibitor for the treatment of a wide range of Bcl-2 positive malignancies.




Sanford Markowitz, MD, PhD, was named winner of the Shaikh Hamdan bin Rashid Al Maktoum award for Medical Sciences for his work on colon disorders and will share a AED 2.8 million prize with 15 other awardees. This award has been consistently acknowledging and celebrating the best scientific and humanitarian works on a global scale, promoting the best practices in health care provision all around the world.




Division of Rheumatology
Ali Askari, MD, Charles Malemud, MD, and Riaz Ahmad, MD, published their work in an article titled "Treatment of SLE and secondary Sjogren's Syndrome with Belimumab" in the Journal of Immunobiology. The results of the small cohort study show that though the use of belimumab as an adjunctive therapy for SLE showed positive changes, sicca symptoms associated with 2°SS did not appear to respond to belimumab.



Charles Malemud, MD, served as an editor for a Springer book titled "Mesenchymal Stem Cells and Immunomodulation." The book explores mesenchymal stem cells and their potential to suppress immune-mediated inflammation.
department conferences & events
Agre Society
Date: January 4
Time: 5:30 - 6:30 p.m.
Location: Carpenter Room
Speaker: Sanford Markowitz, MD, PhD

Grand Rounds
Time: 12 - 1 p.m.
Location: Kulas Auditorium

January 10
"Multiple Myeloma" by Ehsan Malek, MD

January 17
"The Challenge of Cancer Management in Underdeveloped Countries" by Matthew Cooney, MD

January 24

January 31
"Transfusional Medicine" by Moises Auron, MD
department development & diversity
Physician Burnout and Distress: Causes, Consequences, and a Structure for Solutions
Date: Thursday, January 5
Time: 12:00 - 1:00 p.m.
Location: Online webinar
Speaker: Dr. Colin West
Sponsor: Center for the Advancement of Medical Learning
Audience: All faculty and staff interested in the topic

Women Faculty Career Development Programs: Movie Release Party
Date: Wednesday, January 11
Time: 12:00 - 1:00 p.m.
Location: The Louis Stokes Cleveland VA Medical Center, Auditorium K-119
Speaker: Dr. Amy Hise, President, Women Faculty School of Medicine
Sponsor: Women Faculty School of Medicine
Audience: All faculty, male and female, interested in learning about the resources available to them on campus from multiple different organizations for professional development; may be particularly suited to junior faculty

Improving Medical Student Mental Health: A Multifaceted Approach
Date: Thusday, January 12
Time: 12:00 - 1:00 p.m.
Location: Online webinar
Speaker: Dr. Stuart Slavin
Sponsor: Center for the Advancement of Medical Learning
Audience: All faculty and staff interested in this topic; may be of particular interest to educators

Intersectional Feminism: Our Voices Being a Part of the Conversation
Date: Wednesday, January 18
Time: 12:00 - 1:00 p.m.
Location: Tinkham Veale University Center
Sponsor: Case Western Reserve University Flora Stone Mather Center for Women
Audience: All members of the Case Western Reserve University community interested in a discussion of overlapping or intersecting social identities and related systems of oppression, domination, or discrimination

Strategies for Promoting Personal Health and Wellness and Leading Change at the Individual Level
Date: Thusday, January 19
Time: 12:00 - 1:00 p.m.
Location: Online webinar
Speaker: Dr. Catherin Pipas
Sponsor: Center for Advancement of Medical Learning
Audience: All faculty and staff interested in this topic

The Imperative for Incorporating Mind-Body Medicine in Health Professions Education
Date: Thursday, January 26
Time: 12:00 - 1:00 p.m.
Location: Online webinar
Speaker: Dr. Adi Haramati
Sponsor: Center for the Advancement of Medical Learning
Audience: All faculty and staff interested in this topic; may be of particular interest to medical educators