Refresher: What is tuberculosis? (Lee B. Reichman, M.D., M.P.H.)

8/7/2019 Refresher: What is tuberculosis? (Lee B. Reichman, M.D., M.P.H.)

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TB BASICS

Refresher What is tuberculosis?

The Lung Health Program

International Journalists as GlobalHealth Advocates

TB BASICS

Refresher What is tuberculosis?

The Lung Health Program

International Journalists as GlobalHealth Advocates

Lee Reichman, MD, MPHCancun, Mexico

December 1-7, 2009

Lee Reichman, MD, MPHCancun, Mexico

December 1-7, 2009


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TB Historical PermutationTB Historical Permutation

17th - 18th centuries TB took 1 in 5 adultlives

1850 - 1950 one billion people died of TB

Current decade 2000-2010

300 million new infections

90 million new cases

30 million deaths

More people died from TB last year thanany year in history


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TB Could Be EliminatedBecause We Understand It

TB Could Be EliminatedBecause We Understand It

We know its:

Cause Transmission

Treatment

Prevention


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TB Isnt EliminatedTB Isnt Eliminated

Because:

Nobody seems to care

This wouldnt be toleratedfor any other disease


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Deaths Due To:Deaths Due To:

TB (annually) 1,770,000

SARS 813

Avian Influenza 6,250

Anthrax 5

Mad Cow Disease 1 (Cow)

Smallpox 0


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What is Tuberculosis?What is Tuberculosis?

Infectious disease caused by a germ calledMycobacterium tuberculosis

It is spread through the air

Usually affects the lungs although it canaffect any organ

Is spread when someone who is sick withTB disease of the lungs coughs or sneezes,releasing germs and a person nearbybreathes in these infected droplets


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What happens when you

breathe in TB germs? A person infectedwith the TB bacteria is

not necessarily sick

TB infection: The natural defense system cankeep the bacteria under control and person isnot sick

TB disease (active TB) : Immune system

cannot keep the bacteria under control andthey multiply rapidly, making the person sick


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Most effective way to stop

transmission

Most effective way to stop

transmission Isolate patients with suspected or confirmed

TB disease immediately

Start treatmentwith anti-TB medicine

As long as TB patient is onappropriate TB medicines and takes

medications as directed, the potentialto infect other people will declinerapidly.


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Development of TB diseaseDevelopment of TB disease

HIV-negative: about 10% of people infected with TBwill develop TB disease within their lifetime

Anyone can get TB!

However, there are some groups at greater risk fordeveloping TB disease:

People with HIV infection

Those infected in the last 2 years

Babies and young children

People who inject illegal drugs or abuse alcohol People sick with other diseases that weaken the immunesystem

Elderly people


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Diagnosis of TB DiseaseDiagnosis of TB Disease

A person suspected of having TB diseasemay have these symptoms:

Fever, cough (3 weeks), chest pain, nightsweats, weight loss, fatigue, coughing up

blood, decreased appetite

Diagnosis:

Patient history and clinical exam

Laboratory tests Chest x-rays


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Treatment of TB DiseaseTreatment of TB Disease

TB is curable!

TB treatment strategy (DOTS)

Standardized, short-course

Proper patient management

Treatment

6 months

4 antibiotic-drugs for 2 months

2 antibiotic-drugs for 4 months


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TB/HIVTB/HIV

TB/HIV is a lethalcombination, each speedingthe others progress

Risk of progression of TBdisease much greater inHIV-infected persons

About 10% chance everyyear

TB is leading cause of deathin those with HIV


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Co-Existence of HIV & TB infectionCo-Existence of HIV & TB infection

Risk of Active TB

10% per year10% per lifetime

.0017% per year

TB

InfectionHIV

Infection


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HIV Drives the TB Epidemic:HIV Drives the TB Epidemic:

TB Trends in Africa 1980TB Trends in Africa 1980--20062006

0

100

200

00

400

00

600

00

1980 198 1990 199 2000 200

N

tificati

nratea

f

rm

s

Zim a e Ken a a a iTan an ia te d 'Iv ire th Africa


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Drug Resistant TBDrug Resistant TB

Man-made phenomenon

Causes:

Inadequate or incomplete

treatment Interruption in the supply

of essential drugs

Poor quality drugs

Treatment of MDR-TB Very long 18-24 months

Toxic 2nd line drugs

Expensive

Persons at increased risk

With history of TB

treatment Received inadequate

treatment for >2 weeks

Contacts of known drug-resistant patients

Born or living in areaswith high prevalence ofdrug-resistant TB


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Pathogenesis ofDrug Resistance 1

IP

R

INH

RIF

P A

INH II

I

I

I

I


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Pathogenesis ofDrug Resistance 2

INHRIF

I

I

I

I

I

I

I

I

I

I

I

I

I

I

I

I

I

IP

I

IR

IR

IR

IR

IR

IR IR

IR

IRIR

IRIRP

IR


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Unsexy TuberculosisUnsexy Tuberculosis

Concern and attention re: XDR-TB is appropriate, but skips themore important message

XDR-TB, MDR-TB, and drug-sensitive tuberculosis are all thesame disease

The only difference is that MDR-TB is drug-sensitive tuberculosis

modified by inappropriate treatment or drug taking, and XDR-TBis MDR-TB thus modified

We need to recognize that there are more than 9,000,000 newactive drug-sensitive cases of tuberculosis globally that could befeeding drug resistance

It might be a less sexy concept, but they all must be appropriately

treated with current strategies (as well as new diagnostics,drugs, vaccines, and proper infection control measures) to avoidpreventable MDR-TB and XDR-TB, which are always lurking

Preventing active, drug-sensitive tuberculosis, or treating itproperly, should be everybodys priority; it is the only way toprevent MDR-TB and XDR-TB

- Reichman, LB: The Lancet, 2009


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TB Remains a Global KillerTB Remains a Global Killer

Why does TB still infect one-third ofthe worlds population and remain aglobal health threat despite the fact

that highly cost-effective drugs areavailable to eradicate it?


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The Global Burden of TuberculosisNO NEW DRUGS / NO NEW TOOLSThe Global Burden of TuberculosisNO NEW DRUGS / NO NEW TOOLS

Last new drug class specifically for TB -Rifampin (1968 Europe, 197 US)

Most widely used diagnostic test -Tuberculin (1890)

Ineffective most widely used vaccine -

BCG (1919)

Wouldnt one think that largest killer of anysingle infection deserves better, newer tools?


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Approved & Major ExperimentalARV Drugs (1987-2008)

Approved & Major ExperimentalARV Drugs (1987-2008)

ARV Class Approved ExperimentalUnder

Investigation

ExperimentalInterrupted

NRTI 8 12 8

NNRTI 9 6

PI 10 5

Entry Inhibitors 2 17 10

IntegraseInhibitors

1 5 2

MaturationInhibitors

0 3 0

Gene Therapy 0 0

TOTAL 25 55 30

Vitoria MAA, October 2008


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NEW TOOLSNEW TOOLS

There are now 3 major global efforts to alleviatethis problem

Foundation for Innovative New Drugs (FIND)

AERAS Global Vaccine Foundation

Global Alliance for TB Drug Development


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About AerasAbout Aeras

International non-profit organization with 1 current partners,among them:

Crucell NV (Netherlands), Statens Serum Institut (Denmark),GSK (Belgium), Max Planck Institute (Germany), UCLA (USA),University of Cape Town (S. Africa), St. Johns Medical College(India)

Aeras forms joint development teams with partners todevelop promising TB vaccine candidates currently thereare 3 leading candidate regimens

Primary funding provided by the Bill & Melinda GatesFoundation with additional funding from CDC, NIH, andDanida


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The Problem:The Problem:Current TB therapy, though efficacious, is inadequate to control theglobal TB epidemic - too long and too complex

Global Alliance for Tuberculosis

Drug Development

Growing Epidemic

5% increase in annual incidence in Africa

1% increase in annual incidence globally

Current status9 million new cases annually

2 million deaths annuallyReference: Global tuberculosis control: surveillance, planning, financing. WHO

Report 2005.


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The TB AllianceThe TB Alliance

Founded in 2000 (Cape Town Declaration)

Independent Non-Profit Organization

International Public-Private Partnership

Based in New York with offices in Brussels andCape Town


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The TB AllianceThe TB Alliance

Mission

Develop new, better drugs for TB

Ensure affordability, access and

adoption (AAA)

Coordinate and catalyze TB drugdevelopment activities worldwide


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The SolutionThe Solution

New

drugs combined intoshorter, simpler regimens


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1. Active disease

2. MDR-TB

3. TB/HIV co-infection

. Latent infection (LTBI)

TB Alliance PrioritiesBased on impact and feasibility


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Challenges in TB ControlChallenges in TB Control

Insufficient financial and human resources

Inadequate healthcare infrastructure

Weak laboratory capacity and lack of new rapid

diagnostic tools

Lack of new drugs that would cure TB in a shorter time

Lack of effective vaccine that would prevent TB

Poor use of infection control in healthcare settings

Minimal social mobilization for TB control and minimalpopulation awareness stigma

HIV and MDR/XDR threats


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Why do we need to care aboutTB in the rest of the world?

Why do we need to care aboutTB in the rest of the world?


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Lessons from Andrew SpeakerLessons from Andrew Speaker

TB has not gone away, it remains with us, highly prevalent andtransmissible

Anybody can get tuberculosis, not only poor people,minorities, or the foreign-born

TB anywhere is TB everywhere

All resistant TB, MDR and XDR TB is preventable by proper TBdiagnosis and treatment

Good public health is a silent secret, but when there is a small

glitch, it becomes major news

We desperately need new tools for TB diagnosis and treatment

You dont want to sit on an airplane for 8 hours next to anuntreated coughing person with anykind of TB, be it drugsensitive, MDR or XDR


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www.umdnj.edu/globaltb

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Refresher: What is tuberculosis? (Lee B. Reichman, M.D., M.P.H.)

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