Download Responding to STD/HIV Increases and Viagra Use

HIV and TB
Jeffrey D. Klausner, MD, MPH
Professor of Medicine and Public Health
Program in Global Health, Division of Infectious Diseases
David Geffen School of Medicine
Fielding School of Public Health
Special thanks to: Caitlin Reed MD, MPH
Medical Director, Inpatient TB Unit, Olive View – UCLA Medical Center
Los Angeles County Department of Health Services
September 2014
African-American HIV University
Disclosures
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Dr. Klausner is a faculty member of the University of California Los Angeles
Dr. Klausner is a guest researcher with the US CDC Mycotics Diseases Branch
Dr. Klausner is a member of the WHO STD Guidelines group
Dr. Klausner is a board member of YTH, Inc, non-profit
Dr. Klausner is medical advisor for Healthvana.com
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In the past 12 months, Dr. Klausner has received:
– Travel support for meeting coordination and speaking from Standard Diagnostics, Inc.
– Research funding or donated supplies from the NIH, CDC, Hologic, Inc., Alere, Inc.,
Chembio, Inc. Cepheid, Standard Diagnostics, Inc., and MedMira, Inc.
[email protected]
Objectives: TB Update
1)
2)
3)
4)
Review of TB epidemiology & pathogenesis
New tests and treatment for latent TB
Diagnosis of active TB
TB puzzles
TB Frequency
Reported TB Cases, U.S. 1982-2012
CDC MMWR 2010
Where is TB?
Global Tuberculosis Control 2011; WHO
TB is Not Gone
• 1/3 of the world’s population is infected with TB
(Latent TB infection)
• Globally 9 million new cases of active TB / year
• 1.3 million TB deaths / year
Tuberculosis Cases in Foreign-born and U.S.-born
Persons by Race/Ethnicity: California, 2010
Credit: CDPH TB Control Program
Natural History of TB
Exposure
Latent Infection
• Asymptomatic
• Not Infectious
90%
Infection
10%
Close Aerosol Contact
With an Infectious Case
X
Active TB disease
10% lifetime risk
5% first 2 years after
infection
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Treat latent TB to prevent active TB
Relative Risk for Developing
Active TB
Risk Factor
Approximate Risk
by Risk Factors
HIV/AIDS
170 *
Lung Disease due to Silica
30
Immunosuppression
10-15
Cancer
10-15
Hemophilia
5-10
Kidney failure
10-15
Malnutrition
2-4
Diabetes
2-4
Smoking
2
Targeted Tuberculin Testing and Treatment of Latent TB Infection
CDC, MMWR June 2000
Why do HIV-infected patients get TB? *
1) Immune suppression leads to activation of old TB
2) Re-exposure in clinics and hospitals leads to new
infection
Latent TB Infection
Targeted TB screening
1) People at increased risk of recent infection
• Close contacts of active TB case
• Recent immigrants from countries with TB
• Work exposure
– Nursing home, hospital, jail/prison
2) Risk factors for active TB
• Pts with HIV infection
• Other immunosuppressed persons
TB Screening Tests
• Tuberculin skin test (TST)
• Interferon-gamma release assays (IGRAs)
– Quantiferon-Gold In-Tube (Cellestis)
– T. Spot TB (Oxford Immunotect)
• Quantiferon is the most commonly use TB screening
test in patients with HIV-infection *
TB Skin Test
48-72 hrs
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Interpretation depends on risk factors
Reader error
No immune response in some pts
Reactivity
Quantiferon TB Testing
• Measures immune response to TB antigens
• Similar principle to TST
– Uses TB-specific antigens
– Not affected by BCG vaccination (specific)
TST and Quantiferon
Presentation of
mycobacterial antigens
IFN-
TNF-
IL-8, etc.
Tuberculin skin test
IFN-
Antigen
presenting
cell
Memory
T-cell
Andersen P, et al. Lancet 2000;356:1099
TNF-
IL-8, etc.
IGRA
Case 1
• 32 year old health care worker with positive
Quantiferon Test
• Denies cough, fever, weight loss, night sweats
• Chest x-ray negative
• Treat for latent TB infection
– 9 months isoniazid daily or
– 4 months rifampin daily or
– 3 months of isoniazid/ rifapentine weekly
Treatment of latent TB in patients
with HIV infection
• 6 months of isoniazid
• Some recommend 36 months
• ? Perhaps until CD4 > 500
Active TB
Exposure
Latent TB
Infection
Active TB
Infection
Symptomatic
Death
Treatment
TB Diagnostic Tests
• Smear microscopy (sputum, tissue)
• Mycobacterial Culture (sputum, blood, tissue)
• Nucleic Acid Amplification Tests (sputum, tissue)
Sputum Smear Microscopy
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Easy, rapid, cheap
– Sensitivity*:
• In field conditions :
40-60%
• HIV- infected patients: 20-60%
– Specificity: Not specific for M.
tuberculosis
Arrow: Acid Fast Bacilli
*WHO Stop TB Diagnostics Working Group Strategic Plan 2006-2015
Mycobacterial Culture
• Reference Standard for
diagnosis of TB
• Can send from any body site
• Solid or liquid culture medium
• Limitation:
– Slow (mean: 24 days for positives)
– Resource intensive, costly
Drug Susceptibility Culture Testing
• Diagnosis of drug-resistant TB
• Conventional Methods:
– Grow TB in culture
– Assess for growth (resistant)
or absence of growth (susceptible)
at 4 weeks
Nucleic Acid Amplification Tests
– Amplify nucleic acid segments
specific for M. tuberculosis
– Rapid: Results in 24-48 hours
– Commercially Available:
• Mycobacterium Tuberculosis Direct
(MTD)
• Amplicor M.Tb Test (Amplicor)
• Cepheid GeneXpert MTB Rif
Cepheid GeneXpert
MTB Rif
Case 2
• 66 yo homeless man with abnormal chest xray,
weight loss, chronic cough
• Smear positive for AFB
• HIV-infected
• Treatment?
– 4 drug regimen: Rifampin, INH, PZA, Ethambutol
– May stop PZA after 2 months
– May stop Ethambutol if no resistance
– For 6 to 9 months total duration
TB and HIV infection
• Difficult to diagnosis (low amount of TB)
• Drug-drug interactions
• Immune reconstitution inflammatory syndrome (IRIS)
– Delay antiretroviral therapy until on TB treatment
• If CD4 < 50 delay 2 weeks
• If CD4 > 50 and stable, delay 8 weeks
– Monitor for worsening
– Consider addition of steroids
New developments in TB
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Ongoing search for point of care test
– Urine LAM: antigen detection; potentially
useful, in HIV-infected patients with CD4
<50
Reports of ‘Totally Drug Resistant’ TB
Finally, new drugs for drug-resistant TB
– Bedaquiline (Sirturo)–
FDA approved Dec 2012 for MDR-TB
– Delaminid – phase III trial
Olive View Inpatient TB Unit
TB Unit
15 beds (10 staffed currently)
Patients must be stable with labconfirmed TB
Categories of patients
• Infectious, need prolonged
isolation
• Drug resistant TB requiring
special management
• TB drug adverse reactions
• Public health detention
Group questions & dilemmas
Group 1
The patient has HIV infection but his TB skin test is negative
What are 3 possible explanations?
Group 2
A patient has been started on TB medicines. He initially gets better
and then gets worse.
What are 3 possible explanations?
Group 3
• Name 3 groups that are high risk for TB
• Describe 3 ways the risk for TB might be decreased in those
groups?
Group 4
• TB is a public health condition that gets reported to the health
department.
• Name 3 other “reportable” conditions
• Describe what the health department does with that information
Thank you