Tuberculosis

Title

Why Should We Care About TB?

Two  billion  people have latent TB -- about 1/3 of the world’s population!

It kills around two million people annually! In fact, 25% of avoidable death in the working age group is caused by tuberculosis

But…  It is completely curable and relatively inexpensive to treat

by Meredith Maxey [Honors Tutorial college/BIOS]  

References

Ancient History         

Picture:  Hippocrates  Source

  • 4000 BC – Skeletal remains show evidence of TB
  • 3000 BC – Egyptian mummies revealed signs of tubercular decay
  • 2000 BC – Presence in the Americas 
  • 460 BC – Hippocrates identified as “phthisis;” it was the most widespread disease of the time
Modern History

1820s – TB identified as a disease

1839 – “Tuberculosis” named by J. L. Schonlein

1838-1845 – Dr. John Croghan attempts treatment in Mammoth Cave because he thought the constant temperature and purity of the cave would help treat or even cure the disease

1859 – First TB sanatorium opened in Poland

1882 –  Mycobacterium tuberculosis  identified by Robert Koch

1885 – First TB sanatorium in the US opened

1890 – Koch proposes an ineffective remedy to TB involving glycerine extract of the tubercle bacilli

1906 – Calmette and Guerin developed BCG (bacillus of Calmette and Guerin) vaccine

Recent Developments

1921 – BCG vaccine first used on humans             

Late 1940s – BCG gained more global acceptance

Picture:  Girls preparing to be vaccinated  Source

1946 – Streptomycin developed and changed the TB focus from prevention to treatment

1980s – Drug-resistant strains on the rise

1993 – WHO declares a global health emergency

Mycobacterium tuberculosis            

That slow-growing, aerobic bacterium is the cause of tuberculosis.  It divides every 16-20 hours as opposed to most others which can divide every 20 minutes.   Mycobacterium tuberculosis  can survive in a dry state of weeks.  Additionally, it is an “acid-fast bacillus.”  This particular bacterium can be identified by its staining characteristics.  When using the Ziehl-Neelson stain, they stain bright red. 

Picture:  Mycobacterium tuberculosis  Source

Transmission

TB is transmitted via aerosol droplets expelled from people (when coughing, sneezing, spitting, speaking) with  active  tuberculosis  Picture Source 

European TB History

1815 – 25% of deaths in England were TB-related

1880s – Disease established as contagious

1904 – Christmas seal fundraiser in Denmark.  This was one of the first known TB fundraising programs

1908 – 75% of people in sanatoria were dead within 5 years

1913 – Medical Research Council in Britain began their first project -- tuberculosis

1918 – 17% of deaths in France

1950 – TB numbers down from 500 per 100,000 people to 50 per 100,000 people.  These decreases have been attributed to improvements in the public health sector as well as the increased use of antibiotics

2000 – Numbers on the rise as drug-resistant strains become more prevalent

Increased Risk for TB
  • People with HIV
  • People who smoke 20+ cigarett es daily
  • Leading infectious killer of women of reproductive age
  • 5000 die from the disease everyday

Picture:  Man at an increased risk for TB  Source

TB Vaccines:

BCG Vaccine (1921)

  • Bacillus of Calmette and Guerin  

Picture Source

  • Focal point of many TB control programs
  • Administrations were based on criteria such as frequency of exposure opportunities
  • Pulmonary efficacy has been estimated anywhere from 0-80%
  • All other forms of TB are 80% protected against with the vaccine
  • Until 2005, the UK policy was to vaccinate everyone at the age of 12; this was stopped because it was no longer cost effective
New Tuberculosis Vaccines
  • National Institute of Allergy and Infectious Diseases (2004) conducted trials on the first recombinant TB vaccine
  • DNA TB (2005) vaccine given with conventional chemotherapy helped prevent re-infection in mice.  Not likely to be available to humans for another 5+ years
  • MVA85A (genetically modified vaccinia virus) Is a vaccine in phase 3 trials in South Africa by a group from Oxford University
Tuberculosis in Ukraine

Picture Source

Signs and Symptoms
  • Productive, prolonged cough of more than three weeks
  • Chest pain
  • Hemoptysis
  • Systemic symptoms
  • Fever
  • Appetite/weight loss
  • Easy fatigability
Extrapulmonary TB  

Picture:  All the places where one can get TB  Source

25% of tuberculosis cases and can accompany pulmonary TB

  • CNS (meningitis)
  • Lymphatic system (scrofula of the neck, not contagious)
  • Genitourinary system
  • Bones
  • Joints (Pott’s disease)
  • Miliary TB (common in HIV patients, and is especially serious)
Pathogenesis                 
  • Inhalation of bacilli
  • Bacilli trapped by immune system
  • Bacilli sealed up in hard nodular tubercles (cheese-like mass that breaks down the respiratory tissues and forms cavities in the lungs)

Picture:  Representative plate of tubercles and scar tissue in lung  Source

  • Scar tissue can eventually replace the nodules upon treatment       
  • However, once in the blood (which can happen when tubercles break down and release bacilli), TB can travel almost anywhere in the body
  • Death can result from failure of ventilation and general toxemia or exhaustion
There is an increased risk of infection for…
  • Immunocompromised patients (HIV/AIDS)
  • Children of high-risk adults
  • People who inject drugs
  • Healthcare workers
  • Certain racial/ethnic minorities
Diagnosis
  • Tuberculin skin test 

Picture:  Reading of Mantoux skin test  Source

  • Mantoux Skin Test
  • Heaf (used in the UK until 2005)
  • X-ray (never conclusive, only suggestive)

Picture:  Chest X-ray of person with TB  Source

  • Surgical biopsy
  • Microbiologic smears or cultures of sputum
Progression
  • 90% infected have asymptomatic latent TB infection (LTBI)
  • 10% chance of progression to TB disease
  • If untreated, active TB has a death rate of over 50%
  • Interestingly, some rheumatoid arthritis drugs can cause an increased risk of progression.  Those block tumor necrosis factor-alpha, which is an inflammation causing cytokine.  However, cytokines are important in the defense of the immune system against TB.
Treatment

Treated TB has a death rate of < 5%, but one of the main problems faced is that people do not take their medications for the specified length of time.  This is suspected to have played a large role in the current increase of individuals with drug-resistant strains.

Standard treatment for active TB:

  • Isoniazid (1952)  
  • Rifampicin (1963)
  • Pyrazinamide (1954)
  • Ethambutol (1962)

Picture:  Daily dose of TB drugs  Source

  • Take all four for two months, then just Isoniazid and Rifampicin for four more months

Standard treatment for latent TB:

  • Isoniazid – alone for six to nine months

Multidrug-resistant TB (MDR-TB):

  • Resistant to isoniazid and rifampicin

Extensively drug-resistant TB (XDR-TB):

  • Resistant to 3+ of the 6 classes of second-line drugs

The largest reported outbreak of XDR-TB was in KwaZulu-Natal, South Africa where 52/53 people died from the disease.

 

Epidemiology
 

Picture Source

High    ~400 cases per 100,000 people

Low     ~40 cases per 100,000 people

TB Challenges Faced
  • High rate increases of MDR-TB and XDR-TB (mostly in countries of the former Soviet Union)
  • Increase in HIV epidemic leading to increase in TB

Picture Source

  • Reformation of the health sector
  • Limited financial backing
  • Lack of advocacy, communication and social mobilization
WHO and Europe

--European tuberculosis control program + WHO global program:

These two are united to reduce sickness and death caused by TB and to also prevent the spread of MDR-TB with the following activities

1)  Supporting STOP TB strategy by guiding countries in policy development and technical operations

2 ) Helping healthcare professionals develop the technical and managerial skills necessary to deal with TB effectively through the organization of national and international workshops and conferences

3)  Monitoring MDR-TB

4)  Developing guidelines for those involved in TB control activities specifically policy makers, nongovernmental organizations, and donor and health personnel

5)  Coordinating technical agencies and donors globally as part of a global STOP TB movement

Interesting European Facts 

Picture Source

  • Badgers have been identified as vector species; subsequently, the Irish government mounted a campaign to eradicated the species
  • Prizes associated with TB vaccine development
  • Vampire stories with a TB origin due to the fact that TB symptoms were similar to those of a vampire (pale skin, coughing blood, sensitivity to light) 

Picture:  Vampire? Or someone with TB?  Source

 
 
 
Famous Afflicted Europeans
  • John Keats
  • Frédéric Chopin
  • Charlotte, Emily, and Anne Brontë
  • Anton Chekhov
  • Franz Kafka
  • George Orwell

Picture:  The Bronte sisters  Source

TB Statistics in Ukraine                          

Picture:  Ukrainian People  Source

  • 48,000 new cases annually
  • Incidence ~ 100/100,000 people
  • Mortality ~ 15/100,000 people
  • 8.3% of TB cases that are HIV +
  • 10% of new cases are MDR-TB
  • No current 'directly observed therapy, short course' (DOTS) data found
Ukrainian Prisons

Higher risk for developing active TB due to the following problems:

  • Poor infection control
  • Delays in diagnosis
  • Inadequate treatment
  • High prevalence of HIV  
  • Overcrowding and poor nutrition

       Picture:  Ukrainian Prison  Source


TB is not unavoidable in prisons! DOTS can be implemented to help control the spread of TB.  Effective TB control benefits others besides the prisoners.  It helps to protect staff, visitors, and the community at large as well.  There are currently programs in the Ukraine designed for prison managers to train/enable them to help control TB in their prison.

Ukraine and XDR-TB

   Progression of MDR-TB  

  • It has been said that treating MDR-TB is like treating cancer, and XDR-TB is even worse

Picture:  Ukrainian Flag  Source

Highest Concentration is in Western Europe/Asia
  • 69,000 people have died from TB with an estimated 450,000 new cases in 2004 in the WHO European Region
  • WHO organizing a Ministerial Forum in 2007
  • Goals of forum include increasing funding to the European Union
Prevention and Control Strategies

~Four main priorities~

  1. Identify and treat all those who have TB
  2. Find and evaluate those that have been in contact with people with TB (and treat them appropriately)
  3. Test high-risk groups for latent TB and treat before onset of active TB
  4. Maintain surveillance standards (which allows for the tracking of progress)

Picture:  STOP TB Logo  Source

  • Save an additional 14 million lives between 2006-2015

Components of partnership

  • DOTS expansions (the major plank of the program)
  • Control MDR-TB
  • Address high risk groups
  • Engage all care providers
  • Empower those with TB
  • Promote TB Research
Ukraine in the News
  • Ukraine’s Cabinet of Ministers approves plan for national TB program (6-27-06)
  • Ukraine Health Ministry to establish a group working on TB and HIV Project Grant (6-6-06)
  • Ukraine Adopts Resolution to Establish TB, HIV/AIDS Committee (6-2-06)