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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 DiagnosisCommonly 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
0.00 - 0.991.00 - 2.993.00 - 5.996.00 – 10.00>10.00No data
* Sub-national coverage in India, China, Russia, Indonesia.
MDR-TB among new cases 1994-2007
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
Global estimate: about 500,000 new MDR-TB cases a year
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
In former Soviet Union countries, proportions of XDR-TB among MDR-TB range from 4% in Armenia, to almost 24% in Estonia.
WHO estimates around 40,000 XDR-TB cases emerge every year
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 anti-TB drugs for the treatment of MDR-TB
Implementation approaches to Drug-Resistant 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 well-developed 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
TB latent infection HIV infection
2 Billion 33 Million
11 million (Latent TB and HIV co-infected)
No estimate
0–4
20–49
>= 50
5–19
HIV prevalence in TB cases, (%)
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
HIV prevalence among TB cases, 2007
Global estimate: about 1.4 million TB/HIV cases and 450,000 TB/HIV deaths a year
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.