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Practical Considerations of Latent Tuberculosis Infection. Susan Even, MD University of Missouri Sharon McMullen, RN, BSN University of Pennsylvania Brenda Johnston, RN, MSN Oklahoma City University Tim Crump, RN, MSN, FNP University of Portland. Disclaimer.
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Practical Considerations of Latent Tuberculosis Infection Susan Even, MD University of Missouri Sharon McMullen, RN, BSN University of Pennsylvania Brenda Johnston, RN, MSN Oklahoma City University Tim Crump, RN, MSN, FNP University of Portland
Disclaimer The presenters have NO actual or potential conflict of interest in relation to this educational activity or presentation Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
Campus Case • 22 yo Vietnamese female graduate student • Tested during fall orientation • Risk factor – country with high TB incidence • Symptom review – negative • QFT-GIT positive Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
Case management Partnered with local health department Smears negative Culture positive for M. tuberculosis, pan-sensitive Contact investigation - roommates negative initially and 8 weeks Completed 9 month treatment (3 drugs) May 2011 Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
Tuberculosis is a very Ancient Disease Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
Evidence of tubercular decay has been found in Egyptian Mummies. • 3000-2400 BCE Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
Recently, discoveries in the submerged village of Atlit-Yam suggest Tuberculosis was present 7000 BCE Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
Atlit-Yam was a village that now is submerged just off the coast of Israel. • The village dates from the very dawn of Neolithic times, earliest agricultural settlements. • Both skeletal and DNA evidence demonstrate TB in a woman and an infant buried together. Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
TB already established at dawn of agricultural settlements. • DNA supports that human TB was not from Bovine TB. Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
In the 17th and 18th Centuries, Tuberculosis caused up to 25% of all Deaths in Europe Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
In 1854, Herman Brehmer proposed TB was a curable disease. • Established the Sanitorium movement. Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
TB Established as Infectious Disease • In 1882, Robert Koch discovered the bacteria that caused TB • In 1900, he isolated tuberculin from tubercle bacilli, which became the basis of the ppd. Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
Robert Koch Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
BCG • In 1921, the BCG Vaccine was first used in humans, though widespread use did not occur till after WWII. Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
BCG • Most effective against TB Meningitis and Miliary TB. • Most useful in pediatric age group. • Efficacy Varies. Studies in UK consistently have shown protective effect of 60-80%. • Closer to equator, benefit appears less. • Causes false positive TST results. Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
BCG: Method of Administration • TST administered prior to BCG; positive TST contraindicates BCG administration. • Positive TST does not imply immunity, only that there is high probability of severe local reaction. • Intradermal administration. • BCG Leaves a Characteristic Scar, often used as proof of prior immunization. Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
Effect of BCG on TST • The effect on TST of BCG received in infancy is minimal, especially > 10 years after vaccination • BCG received after infancy produces more frequent, more persistent and larger TST reactions. Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
Medications to Treat Tuberculosis • In 1946, Streptomycin was introduced as the first antibiotic to be effective against TB. • In 1952, Isoniazid (INH) was introduced. Originally an antidepressant. • While initial results were dramatic, resistance was soon noted to develop. • As other TB antibiotics were discovered, it was noted that combination therapy prevented or slowed the development of resistance. Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
Selman Waksman Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
Burden of Tuberculosis • In 2008, WHO estimated that 1/3 of the global population is infected with TB. • In 2005, 1.6 million people died of TB. • The emergence of drug-resistant organisms threatens to make TB once again an incurable disease. Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
“High Incidence” Countries are defined as areas with reported or estimated incidence of ≥20 cases per 100,000 population Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
Afghanistan, Algeria, Angola, Argentina, Armenia, Azerbaijan, Bahrain, Bangladesh, Belarus, Belize, Benin, Bhutan, Bolivia (Plurinational State of), Bosnia and Herzegovina, Botswana, Brazil, Brunei Darussalam, Bulgaria, Burkina Faso, Burundi, Cambodia, Cameroon, Cape Verde, Central African Republic, Chad, China, Colombia, Comoros, Congo, Cook Islands, Côte d'Ivoire, Croatia, Democratic People's Republic of Korea, Democratic Republic of the Congo, Djibouti, Dominican Republic, Ecuador, El Salvador, Equatorial Guinea, Eritrea, Estonia, Ethiopia, French Polynesia, Gabon, Gambia, Georgia, Ghana, Guam, Guatemala, Guinea, Guinea-Bissau, Guyana, Haiti, Honduras, India, Indonesia, Iraq, Japan, Kazakhstan, Kenya, Kiribati, Kuwait, Kyrgyzstan, Lao People's Democratic Republic, Latvia, Lesotho, Liberia, Libyan Arab Jamahiriya, Lithuania, Madagascar, Malawi, Malaysia, Maldives, Mali, Marshall Islands, Mauritania, Mauritius, Micronesia (Federated States of), Mongolia, Montenegro, Morocco, Mozambique, Myanmar, Namibia, Nepal, Nicaragua, Niger, Nigeria, Pakistan, Palau, Panama, Papua New Guinea, Paraguay, Peru, Philippines, Poland, Portugal, Qatar, Republic of Korea, Republic of Moldova, Romania, Russian Federation, Rwanda, Saint Vincent and the Grenadines, Sao Tome and Principe, Senegal, Serbia, Seychelles, Sierra Leone, Singapore, Solomon Islands, Somalia, South Africa, Sri Lanka, Sudan, Suriname, Swaziland, Syrian Arab Republic, Tajikistan, Thailand, The former Yugoslav Republic of Macedonia, Timor-Leste, Togo, Tonga, Trinidad and Tobago, Tunisia, Turkey, Turkmenistan, Tuvalu, Uganda, Ukraine, United Republic of Tanzania, Uruguay, Uzbekistan, Vanuatu, Venezuela (Bolivarian Republic of), Viet Nam, Yemen, Zambia, Zimbabwe Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
“Low Incidence” Countries are defined as areas with reported or estimated incidence of <20 cases per 100,000 population Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
Albania, Andorra, Antigua and Barbuda, Australia, Austria, Bahamas, Barbados, Belgium, British Virgin Islands, Canada, Chile, Costa Rica, Cuba, Cyprus, Czech Republic, Denmark, Dominica, Egypt, Fiji, Finland, France, Germany, Greece, Grenada, Hungary, Iceland, Iran (Islamic Republic of), Ireland, Israel, Italy, Jamaica, Jordan, Lebanon, Luxembourg, Malta, Mexico, Nauru, Netherlands, New Zealand, Norway, Oman, Puerto Rico, Saint Kitts and Nevis, Saint Lucia, Samoa, Saudi Arabia, Slovakia, Slovenia, Spain, Sweden, Switzerland, United Arab Emirates, United Kingdom, United States of America, West Bank and Gaza Strip Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
Screening our Students • ACHA Recommendations • Screening vs. Testing Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
Increased Risk For Tuberculosis Infection (Population risks): • Foreign-born persons who have immigrated within the last 5 years from countries with high incidence of TB disease • Persons with a history of travel to/in areas with a high incidence of TB disease • Persons with signs and symptoms of active TB disease • Close contacts of a person known or suspected to have TB disease • Employees, residents, and volunteers of high-risk congregate settings (e.g., correctional facilities, nursing homes, homeless shelters, hospitals, and other health care facilities) • Some medically underserved, low income populations as defined locally • High-risk racial or ethnic minority populations defined locally as having an increased prevalence of TB disease • Persons who inject illicit drugs or other groups of high-risk substance users (e.g., crack cocaine) Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
What are Schools Doing? • Informal study via SHS • Some schools following ACHA Guidelines and screening all students and testing appropriately. • Some schools are testing certain higher risk populations who are easily mandated for testing (International, health-care, education students). • Some schools do not require asymptomatic testing. Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
Why should we care about Tuberculosis Screening? Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
Identify, Treat, and Minimize Transmission of Active TB Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
Also Important: Identify and Treat Latent TB • 10% of persons with Latent TB will develop Active TB at some point in their life. • 80% of Active TB in the US is from reactivation of previous disease. • Nearly all of those cases could have been prevented by prior administration of prophylactic treatment of latent infection. Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
TUBERCULIN SKIN TEST Also known as PPD (Purified Protein Derivative) Or Mantoux Test Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
I’m Preaching to the Choir Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
Purpose of the TST • PPD (Mantoux) is indicated for the detection of a delayed hypersensitivity reaction to tuberculin as an aid in the detection of infection with Mycobacterium tuberculosis Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
History of the TB Skin Test • Test created in 1907 by Charles Mantoux in France, modified in 1939 in USSR • Used worldwide, largely replacing Tine test • Tuberculin is a glycerol extract of the tubercle bacillus • PPD is precipitate of molecules obtained from filtrates of sterilized concentrated cultures Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
Indications for use • Immigrants from countries where prevalence of TB is high • Risk of reactivation due to impaired immunity • Healthcare workers • Travelers at risk from travel in high-endemic countries • Staff members in correctional facilities Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
Methodology of TST • 0.1 ml (5 TU) • Injected intradermally with ¼ to ½” needle, usually anterior surface of forearm • Requires producing wheal of 6 to 10 mm • Read at 48-72 hours Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
Why and how does this test work? • After initial exposure with M. Tuberculosis, sensitization occurs primarily in regional lymph nodes • T lymphyocytes proliferate in response to the antigenic stimulus • Subsequent re-stimulation by PPD evokes a local reaction mediated by these cells • Incubation of 2 to 12 weeks usually necessary after exposure to TB in order for result to be positive. Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
Two-Step Testing Not a test of dance skills! 2-step used to detect individuals with past TB infection who now have diminished skin test reactivity • Reduces the likelihood that a boosted reaction is later interpreted as a new infection • 2-step testing is indicated as initial test for persons who will be retested periodically, such has health profession workers. (not indicated if IGRA available) • Method: A second TST is placed 7 days after first • Abbreviated method: first test read 7 days after placing it and 2nd test administered during same visit. Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
Interpretation • Read at 48-72 hours • Induration is produced through vasodilatation, edema, fibrin deposition and other inflammatory cells • Measure induration transversely across the forearm Result is positive if: >5mm in immunocompromised persons or those who have had recent close contact with active TB >10 mm if born in countries in Asia, Africa, Caribbean, Latin America or high-risk communities. Also healthcare workers >15 mm if general population with no other risk factors Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
False Negatives Can be caused by: • Viral infections such as MMR, chickenpox and HIV • Live virus vaccinations given within 1 month • Active TB • Immunosuppressive agents • Malignancy Even-McMullen-Johnston-Crump, ACHA, 6.2.2011
Documentation • Document: Date, brand, lot number, expiration date, result in mm • Provide patient with documentation of date and result in mm • Do not accept documentation stating “positive” or “negative” • Most Universities do not accept testing beyond 1 year Even-McMullen-Johnston-Crump, ACHA, 6.2.2011