Download TB 101 presentation

TB 101
Erin E. Howe, Public Health Watch
[email protected]
Objectives
1. Understand key clinical features of TB infection
& disease, MDR-TB and TB/HIV.
2. Introduce the epidemiology and control
strategies for TB, MDR-TB and TB/HIV.
3. Discuss TB in PHP’s geographic focus areas
and how it impacts injection drug users and
people living with HIV.
4. Two intersections between TB and human
rights.
Why should we care about TB?
• One-third of the world’s population is infected
with latent tuberculosis (TB)*
• There were an estimated 9.27 million new cases
of TB in 2007 including 1.37 million HIV-positive
cases (14%)
• Leading killer of people with HIV/AIDS globally,
accounting for almost 25% of all HIV deaths in
2007
• An estimated 511 000 new cases of multi-drug
resistant TB occurred in 2007, about 10% of
whom had extensively drug-resistant TB
*Latent TB will be defined in upcoming slides.
Relevant Terms for TB Data
Prevalence total number of cases of a
disease in a population at a given time
Incidence number of new cases of a
disease in a population during a particular
time period (per year)
HIV is most often measured using
prevalence, while TB is measured using
incidence.
Number of new TB cases
Proportion of new TB cases per
100,000
TB transmission
TB is contracted by inhalation of aerosolized
infected particles (droplet transmission)
•One cough produces 500 droplets
•The average pulmonary TB
patient generates 75,000 droplets
per day before therapy
•Falls to 25 infectious droplets
per day within two weeks of
effective therapy
TB infection vs. TB disease
Latent TB infection (LTBI) refers to the period of
time when the immune system has been
successful in containing TB and preventing
disease. Someone with LTBI is not infectious,
will not feel sick and has a normal chest x-ray.
Active TB disease refers to the time when TB
breaks out of latency, begins multiplying and
causes disease. Someone with active TB may
feel sick and is contagious.
Progression from infection to
disease
•
•
•
•
•
•
HIV infection
Immunosuppression
Recently infected with TB
Injection drug and/or substance use
History of inadequate TB treatment
Underlying medical conditions (malnutrition,
diabetes, silicosis, cancer, etc.)
• Stress
Symptoms of Active TB
•
•
•
•
•
•
Persistent cough
Weight loss
Fever
Night sweats
Shortness of breath
Swollen glands (particularly in neck,
armpits)
• Fatigue
Pulmonary vs. Extra-pulmonary TB
• Pulmonary: lungs
– Contagious
– 80-85% of cases
• Extra-pulmonary: pleura, central nervous
system, lymphatic system, genitourinary
system, bones and joints, disseminated
(miliary TB)
– Less contagious
– 15-20% of all TB cases
– >50% of TB/HIV cases
TB Diagnosis
Used primarily in low incidence/high resource settings:
• TST/PPD/Mantoux/Skin test- injecting tuberculin PPD
into the inner surface of the forearm, result can
measured between 48 and 72 hours
– Few false negatives
– Many false positives due to the interaction with BCG vaccine
• Interferon Gamma Assays (ELISPOT, Quantiferon-Gold)blood test that results in a quantitative result
– Few false negatives and positives
– Blood needs to be processed within 12 hours
– Currently being studied in HIV-positive individuals & children
TB Diagnosis
Commonly used in low-resource settings:
• Sputum/AFB Smear (pulmonary TB)- patient produces a
sample by coughing up sputum from deep in their lungs
– Sputum smear positive- acid fast stain colors TB bacilli present
on slide
– Sputum smear negative- acid fast stain does not show TB bacilli
• Clinical/Symptom-based
– Using WHO’s smear-negative algorithm
– Possible to screen for extra-pulmonary TB symptoms
• Imaging Methods (x-ray, fluoroscopy*)- pulmonary TB
*shows results in real time; more economical, simple and rapid than x-rays but less
sensitive; useful for mass screening; greater exposure to radiation
TB Diagnosis
Used as secondary methods or in areas with increased
lab capacity:
• Culture (“Gold Standard”)
– Detects extrapulmonary TB
– Few false negatives and positives
– Takes 4-6 weeks
• Molecular Methods (PCR, etc.)
– For extra-pulmonary TB, sample may to be cultured first
– Few false negatives and positives
– Expensive; Require increased laboratory capacity
TB Treatment
• Standard drug susceptible regimen: Isoniazid
(INH), Rifampin/Rifampicin (RIF), Ethambutol
(EMB), Pyrazinamide (PZA)
• The last new TB drug was developed over 50
years ago
• DOT (Directly Observed Therapy): a
treatment approach that involves a health
care provider or trained layperson to observe
patients ingesting TB medications, monitor
side effects and assess clinical improvement
DOTS TB Control Strategy
1. Political commitment with increased and sustained financing
2. Case detection through quality-assured bacteriology
3. Standardized treatment, with supervision and patient support
4. An effective drug supply and management system
5. Monitoring and evaluation system, and impact measurement
Drug Resistant TB
MDR/XDR-TB
• MDR-TB is a form of TB that does not respond to
treatment using first line-drugs and is resistant to at
least isoniazid and rifampin. It can take two years to
treat with drugs that are more toxic and can be 100
times more expensive than first-line treatment
• XDR-TB is resistant to at least the two most
powerful first line drugs (isoniazid and rifampin) and
several second line drugs (flouroquinolones plus at
least one of the second-line injectables)
How does drug resistance
develop?
System-related causes:
• Inadequate treatment regimen
• Poor case management– adding a single drug to
a failing regimen
• Lack of or delayed drug susceptibility testing
• Insufficient system support (cost, transportation,
education)
Patient-related cause:
• Patients do not complete/adhere to a full course
of TB treatment
How is drug resistance diagnosed?
• Inadequate or lack of clinical improvement
on current TB treatment regimen
• Drug Susceptibility Testing- identifies
resistance to both first and second line TB
drugs allowing a therapeutic regimen to be
identified
– Culture
– Molecular diagnostic methods
MDR-TB among new cases 1994-2007
Global estimate: about 500,000 new MDR-TB cases a year
* Sub-national coverage in India,
China, Russia, Indonesia.
0.00 - 0.99
1.00 - 2.99
3.00 - 5.99
6.00 – 10.00
>10.00
No data
The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World Health Organization
concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps
represent approximate border lines for which there may not yet be full agreement.
 WHO 2006. All rights reserved
WHO MDR-TB Survey
•
•
•
•
Data from 81 countries and 91,577 patients
Collected in 2002-2006
MDR-TB, on average, in 5.3% of all TB cases
Study represents a fraction of MDR-TB cases
– No extrapulmonary cases
– Only 35% of all notified smear-positive TB cases
• Trend data only available from 47 countries
• Only 6 countries in Africa were able to provide
data due to lack of laboratory capacity to
diagnose MDR-TB
14 Places with
MDR-TB Rates >6%*
1. Azerbaijan, Baku City (22.3%)
2. Moldova (19.4%)
3. Ukraine, Donetsk (16%)
4. Russia, Tomsk (15%)
5. Uzbekistan, Tashkent (14.8%)
6. Estonia (13.3%)
7. Russia, Mary El (12.5%)
8. Latvia (10.8%)
9. Lithuania (9.8%)
10.Armenia (9.4%)
11.Russia, Orel (8.8%)
12.China, Inner Mongolia (7.3%)
13.China, Heilongjiang (7.2%)
14.Georgia (6.8%)
* Among new cases; Some are countries and some are sub-sections due to
lack of complete surveillance data.
XDR-TB Cases Confirmed in 45
Countries
WHO estimates
around 40,000
XDR-TB cases
emerge every year
In former Soviet Union countries, proportions of XDR-TB among MDRTB range from 4% in Armenia, to almost 24% in Estonia.
WHO’s TB Control Strategies:
Applied to Drug Resistance
• Strengthen standard DOTS programs to
ensure completion of therapy for drug
susceptible TB and prevent the development
of resistance
• Customize DOTS Framework (DOTS-Plus) to
address drug resistant TB
– WHO’s Green Light Committee (GLC)
Initiative: Mechanism that enables access
to affordable, high-quality, second-line antiTB drugs for the treatment of MDR-TB
Implementation approaches to DrugResistant TB Treatment
• In-Patient Care- patients receive treatment in hospitals
or care facilities for all or part of their treatment
– Ensures adherence while in facility
– Costly
– Potentially increases stigma
• Community-based care- patients receive TB
medications in the community, either at a local clinic or
through a home visit from a community health worker
– Partners in Health as key implementer (model program in Peru)
– OSI-funded program in Lesotho
•
•
•
•
Low default rate
Cost effective
Reduces stigma
Utilizes local community health workers to provide care
IDUs’ TB Risk*
• Injection drug use is associated with higher
prevalence of latent TB and incidence of TB
disease
• Opiates can impair the immune response,
increasing the risk of progression from TB
infection to disease (Also HIV co-infection)
• Factors associated with injection drug use
(homelessness, incarceration, etc.) contribute to
delayed diagnosis (prolonged infectiousness),
longer period to achieve a negative culture and
increased risk for mortality
*Many of the risks, barriers to care and TB program and treatment considerations
apply to all drug users, but the review article source for this information focused
specifically on IDUs.
IDUs’ Barriers to TB Care
• Decreased health-seeking behavior
(discrimination, lifestyle stresses)
• Access to TB clinics is impeded by lack of
availability within harm reduction services
• Opiates suppress cough
• Lack of knowledge about TB (know they
are at increased risk, but not aware of
symptoms, potential resistance or the
difference between infection and disease)
IDUs’ Barriers to TB Care
• Lack of integration of HIV, TB and drug
treatment services
• Denial of drug treatment based on TB
disease or denial of TB treatment based
on drug use
• HIV, homelessness, alcoholism and
injection drug use have been identified as
indicators for poor adherence to TB
treatment
IDUs’ TB Treatment Considerations
• Standard TB treatment regimens can be
hepatotoxic
• Rifampin reduces the half-life of
barbituates and methadone (doses may
need to be increased)
• Rifabutin, a more expensive alternative to
rifampin, has been found to have no effect
on methadone and is also the preferred
substitute for patients on HAART
TB Program Considerations:
IDUs
• DOT improves adherence for IDUs,
particularly when combined with drug
treatment
• Latent TB and TB treatment have been
successful when combined with harm
reduction initiatives
• TB providers need to “meet drug users
where they’re at” to improve adherence
rates and decrease transmission
TB and Prisoners
• High levels of MDR-TB have been reported from
some prisons with up to 24% of TB cases
suffering from MDR forms of the disease
• Several countries in Eastern Europe have welldeveloped TB treatment programs in prisons (i.e.:
Azerbaijan, Moldova), but continuity of care for
those released is poor, which can create drug
resistance
• Pretrial detention has been identified as a key
site for TB transmission due to poor infection
control
TB/HIV
Latent TB and HIV Infection
11 million (Latent TB and HIV co-infected)
TB latent infection
2 Billion
HIV infection
33 Million
HIV prevalence among TB
cases, 2007
Global estimate: about 1.4 million TB/HIV cases and 450,000 TB/HIV deaths a year
HIV prevalence in
TB cases, (%)
No estimate
0–4
5–19
20–49
>= 50
The boundaries and names shown and the designations used on this map do not imply the expression of any opinion whatsoever on the part of the World Health
Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries.
Dotted lines on maps represent approximate border lines for which there may not yet be full agreement.
 WHO 2009. All rights reserved
Challenges in Addressing TB in
PLWHA
• People living with HIV are 20-30 times more likely to
develop TB than those without HIV
• TB is more challenging to diagnose in PLWHA
– >50% of TB/HIV cases are extra-pulmonary
– PLWHA may not have positive sputum smears or a productive
cough
• TB treatment regimens must be customized for PLWHA
on ART because of drug interactions (i.e.: rifampin
affects how some HIV drugs are metabolized)
• When to initiate TB drugs and ART for a patient needing
both can be complicated. There is new evidence that
early initiation of ART (not waiting until TB treatment is
stabilized) is recommended
WHO Interim Policy on TB/HIV
Collaborative Activities
A. Establish the mechanism for collaboration
B. To decrease the burden of TB in PLHIV (3I’s)
C. To decrease the burden of HIV in TB patients
• In 2007, 44 of the 63 TB/HIV high burden
countries had developed a joint coordinating body
and 42 had developed a joint coordinating plan.
• In 2007, 16% of TB cases were tested for HIV,
which accounted for 96% of the total estimated
HIV-positive TB cases.
• The TB program has implemented measures to
address HIV in TB patients, while the HIV
program lags in their implementation of the 3I’s.
WHO Recommended Activities for
Decreasing the Burden of TB in
PLWHA
Intensified Case Finding (ICF)
Isoniazid Preventative Therapy (IPT)
Infection Control (IC)
WHO policy on
Intensified Case Finding
•
TB screening in all HIV service settings using, at a
minimum, a simple set of questions asked by trained
counsellors.
•
A referral system should be established between HIV
services and TB diagnostic and treatment services.
•
TB screening among PLHIV in clinics and hospitals,
household contacts, populations at high risk for HIV,
and congregate settings on a regular basis.
Intensified Case Finding
Implementation
2.2% of PLWHA were screened for TB in 2007
Why is this number so low?
•HIV programs are not adopting intensified case
finding for people living with HIV.
•Lack of a standardized screening tool to detect TB
among PLWHA
IPT
• Isoniazid (INH) is one of the 4 drugs used
to treat TB
• Used to treat latent TB
– 6-9 month treatment course
– Cheap, relatively non-toxic
and well tolerated
IPT Uses
• Prevent active TB in people living with HIV
• 80% reduction in active TB in patients on IPT and
ART
• Greater than 60% reduction in people living with HIV
not on ART (ART alone reduces TB risk by greater
than 50%)
• High risk populations (health care workers, new
immigrants from a TB endemic country,
contacts to an active case, injection drug users,
etc.)
IPT Implementation
0.1% of those eligible for IPT received this treatment
Why is this number so low?
•HIV programs are not adopting IPT for people
living with HIV.
•Common reasons cited for not implementing IPT:
poor adherence, potential toxicity, unnecessary for
people on ART, cost, complication, hard to rule our
active TB, possible creation of drug resistance
•Numerous studies to date, including a Cochran
review article, indicate that IPT does not cause drug
resistance
Infection Control
• Primary prevention method to keep those who
are uninfected free from infection
• Measures to prevent transmission of infectious
germ from a source to others
– Examples: triage patients, adjust clinic schedule,
ventilation, masks, UV lights, outdoor sputum
collection, cough monitors
• Development of national TB infection control
guidelines and a mechanism for developing an
infection control committee and plan at the
health care facility level are key modes of
evaluation
TB and Human Rights
• Detention of drug-resistant TB patients in
South Africa
– Ad hoc (Approximately 1700 beds, over 8,200
estimated drug resistant TB cases in 2007)
– Not of limited duration or subject to review or
appeal
– Protections in conditions where rights are
restricted are not fulfilled (Siracusa Principles)
TB and Human Rights
• Right not to be infected with TB while
being held in prison or pre-trial detention
– Facility conditions should attempt to reduce
TB transmission
– Marginalized populations incur the greatest
burden (injection drug users, sex workers,
migrants, indigenous populations, etc.)
We cannot win the battle against
AIDS if we do not also fight TB.
-Nelson Mandela
Acknowledgements/Sources
• Treatment Action Group (TAG)
• Consortium to Respond Effectively to the AIDS/TB
Epidemic (CREATE)
• Francis J. Curry National TB Center
• Global tuberculosis control - epidemiology, strategy,
financing, WHO, 2009.
• Anti-tuberculosis drug resistance in the world, Report no.
4, WHO, 2008.
• Deiss, et al. Tuberculosis and Illicit Drug Use: Review
and Update CID. 2009 January 1;48: 72-82.
• Golub JE, et al. The impact of ART and isoniazid
preventive therapy on TB incidence in HIV-infected
patients in Rio de Janeiro, Brazil. AIDS. 2007 Jul
11;21(11):1441-8.