TB/HIV: A GLOBAL HEALTH EMERGENCY AND WHAT K-RITH IS DOING ABOUT IT - WILLIAM BISHAI, MD, PHD K-RITH DIRECTOR

TB/HIV: A GLOBAL HEALTH EMERGENCY
                    AND WHAT K-RITH IS DOING ABOUT IT

William Bishai, MD, PhD
K-RITH Director

1993: WHO DECLARES TB TO BE A “GLOBAL HEALTH EMERGENCY”

TB: A BACTERIAL, AIRBORNE INFECTION SPREAD PERSON-TO-
PERSON

•   8 – 10 M new TB cases / year

•   500,000 new MDR‐TB cases
     • 24 months to treat
     • 25% fatal US
     • 95% fatal South Africa

•   50,000 new XDR‐TB cases
     • 24‐48 months to treat
     • 60% fatal US
     • 98% fatal South Africa

TB: “A GLOBAL HEALTH EMERGENCY”, INVISIBLE IN THE WEST

   Record highs worldwide     Record lows in USA + Europe
    Global TB (cases)
                                 TB in England & Wales (deaths)
                                            M.tb.
                                         discovered    BCG
                                                      Vaccine    TB
                                                                Drugs

TB cases & deaths are rising globally, but declining in the West

REPORTED TB CASES PER 100,000 PEOPLE

KWAZULU-NATAL AT THE EPICENTRE

                            •    Population 10 million
                            •    17% general HIV prevalence
                            •    70‐80% of TB patients are HIV infected
                            •    40% of pregnant women are HIV positive
                            •    120 000 notified TB cases/year
                            •    2.3% of all TB is MDR‐TB
                            •    9.8% of MDR‐TB is XDR

NEW TB CASES VS % OF ADULTS WITH HIV

TB AND HIV

HIV infection:
•   Increases susceptibility to TB
•   Accelerates progression of TB
•   Results in atypical presentations of TB symptoms
•   Is associated with extra‐pulmonary TB
•   Is associated with higher TB mortality

TB‐Associated Immune Reconstitution Inflammatory Syndrome (IRIS): a clinical
deterioration after the initiation of anti‐retroviral therapy due to inflammatory
responses against M.tb.

MDR/XDR TB IN TUGELA FERRY : 2005 – 2006

•   53 cases XDR TB
     • All tested HIV+
     • 98% rapid mortality

HIV AND MDR-TB THREATEN TO REVERSE A HALF-CENTURY OF
PARTIAL CONTROL OF TB

In roughly 55 years, we have squandered our precious legacy of
chemotherapy for . . . TB.
--M. Iseman, Jan 2008

1. WE NEED NEW TOOLS . . .
   SCIENCE AND TECHNOLOGY HOLD THE KEYS

We are using antiquated tools
• Diagnostics: same as 1900
• Vaccine: 1921
• Drugs: last new class 1967

WE NEED TO MOBILIZE RESOURCES BETTER

             GFATM Expenses by Disease: 2006‐2009

K-RITH: A REVOLUTIONARY APPROACH TO GLOBAL HEALTH

K-RITH HISTORY

2006:     HHMI Board seeks global
          health initiatives

2008:     UKZN – HHMI letter of
          understanding

2009:     Formal announcement of
          K‐RITH

2009‐10: Building design and Director
         appointment

                                        UKZN Vice Chancellor Malegapuru William Makgoba,
                                                  HHMI President Thomas Cech
                                                          March 2009

HHMI COMMITMENT TO K-RITH

2008-2018:    HHMI commitment of $70 M

After 2018:   Independent, S. African leadership

K-RITH VISION – SHORT TERM

•   Faculty recruitment
•   Building
•   Clinical samples

K-RITH VISION – INTERMEDIATE TERM

•   Biomarker / Diagnostics Discovery
•   Link technology hubs with clinical need
•   Establish strong basic science labs at K-RITH

K-RITH VISION – LONG TERM

• Nurture local basic science, self-sustaining
• Local discoveries drive translational studies for TB-HIV

THE SCIENCE

K-RITH is interested in studying all aspects of TB, HIV and HIV/TB co-infection:

•   Diagnostics and biomarkers
•   Microfluidics
•   Sequencing the genomes of multidrug-resistant TB
•   Characterising the human immune response to TB and HIV
•   Improving the clinical management of TB/HIV co-infected patients

Focus on basic science
• Microbiology
• Immunology
• Pharmacology
• High-throughput biology
• Clinical studies

K-RITH ORGANIZATION
                                    HHMI        UKZN

                                                               Scientific Advisory
                                    Board of Directors
                                                                     Board

Search Committee                        Director

                            K-RITH, Non-Profit Corporation

         Project Leaders          Core Facility Directors             Administration

~10 slots available        1.   Clinical Core
                           2.   Microbiology Core
                           3.   Immunology Core
                           4.   Pharmacology Core
                           5.   High Throughput Biology Core

K-RITH’S EIGHT INVESTIGATORS

      William R. Bishai, M.D., Ph.D. – K-RITH Director
      Joined: September 1 ,2010
      Uses genetic techniques to investigate how M.tb. can slip under the radar of the human
      immune system.

      Adrie Steyn – K-RITH Investigator
      Joined: June 1, 2011
      A native of Cape Town, Steyn studies basic TB biology and diagnostics.

      Alexander Pym – K-RITH Associate Investigator
      Joined: November 14, 2011
      Pym works on improving treatment for people with TB and HIV by studying mechanisms
      of drug resistance.

      Jacques Grosset, M.D. – Scientist in Residence
      Joined: October 1, 2011
      A long-time TB researcher, Grosset tests new drug candidates to help shorten TB
      treatment and find new medicines to fight drug resistant TB.

K-RITH’S EIGHT INVESTIGATORS CONTINUED

       Alasdair Leslie – K-RITH Assistant Investigator
       Joined: August 1, 2012
       Leslie studies the response of immune cells in the first critical minutes when HIV or TB
       invades the body.

       Frederick Balagadde – K-RITH Assistant Investigator
       Joined: July 1, 2012
       Ugandan born Balagaddé uses microfluidics to design microchips that have the potential
       to conduct 100s of clinical tests simultaneously on technology the size of postage stamp.

       Thumbi Ndung’u, Ph.D.
       Will join: October 1, 2012
       Ndung'u, is a native Kenyan interested in understanding antiviral immune mechanisms
       and viral adaptation in HIV as a pathway to vaccine development.

       Alex Sigal – K-RITH Assistant Investigator
       Will join: October 5, 2012
       Sigal is interested in what makes some diseases chronic. Never fully cleared by the
       immune system, they persist at low levels as an intra-patient reservoir; he wants to
       understand why.

K-RITH HAS ESTABLISHED RELATIONSHIPS WITH A VARIETY OF
CLINICAL SITES IN KWAZULU-NATAL

•   Prince Cyril Zulu Communicable Diseases Centre
•   McCord Hospital
•   King Edward VIII Hospital
•   Prince Mshiyeni Hospital
•   King George V Hospital
•   Edendale Hospital
•   Greys Hospital in Pietermaritzburg

EDUCATION AND TRAINING INITIATIVES

• Research opportunities for Masters and PhD students
• Lectures, workshops, and symposia

                                                         TB African Academic Initiative

 Mycobacterial Genetics Course                    Intensive Course in Basic Immunology

OUR MISSION IS TO TRAIN A FUTURE GENERATION OF SCIENTISTS
WHO WILL BE THE NEXT LEADERS OF SCIENCE IN SOUTH AFRICA

                                          Biostatistics Course

UMKHUMBANE SCHOOLS PROJECT

•   Improve mathematics and science education at five disadvantaged high schools in
    Cato Manor
•   After‐school tutoring                       Maths and Science for South Africa’s Future
•   Science clubs                   The UMKHUMBANE SCHOOLS Project
•   Teacher training.

THANK YOU FOR SPENDING TIME WITH K-RITH