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TB and Drug Resistant TB Case Studies. Philip W. Smith, MD Chief, Infectious Diseases University of Nebraska Medical Canter. Reported TB Cases United States, 1953 - 1998. 100,000. 70,000. *. 50,000. Cases (Log Scale). *. 30,000. 20,000. 10,000. 53. 60. 70. 80. 90. 98. Year.
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TB andDrug Resistant TBCase Studies Philip W. Smith, MD Chief, Infectious Diseases University of Nebraska Medical Canter
Reported TB Cases United States, 1953 - 1998 100,000 70,000 * 50,000 Cases (Log Scale) * 30,000 20,000 10,000 53 60 70 80 90 98 Year *Change in case definition
TB Resurgence Increased number of immigrants from countries with many cases of TB HIV / AIDS Epidemic Poor compliance with treatment regimens Increased poverty, injection drug use, and homeless
Number of TB Cases inU.S.-born vs. Foreign-born Persons United States, 1993–2005* No. of Cases *Updated as of March 29, 2006.
Tuberculosis Mycobacterium tuberculosis • Humans main reservoir • Inhalation of droplet nuclei • Most infected without disease • 5-15% develop disease • Greatest risk first two years
Findings of Pulmonary TB • Cough • Fever • Weight loss • Hemoptysis • Night sweats • Chest pain • X ray shows: • Infiltrate • Cavity • Upper lobe location
Transmission of M. tuberculosis • Spread by airborne route; droplet nuclei • Transmission affected by • Infectiousness of patient • Environmental conditions • Duration of exposure • Most exposed persons do not become infected
Administering the TST • Inject 0.1 mL PPD intradermally • Should produce wheal of 6–10 mm • Do not recap, bend, break, remove needles from syringes • Follow standard IC precautions
Reading the Tuberculin Skin Test • Read reaction 48-72 hours after • injection • Measure only induration • Record reaction in millimeters
Interpreting TST Result (2) Different cut points used depending on • Patient’s risk for having LTBI • Size of induration
AFB smear AFB (shown in red) are tubercle bacilli
Cultures • Use to confirm diagnosis of TB • Culture all specimens, even if smear negative • Results in 4 to 14 days when liquid medium systems used Colonies of M. tuberculosis growing on media
TB therapy-general principles • TB is treated much longer than most other bacterial infections, usually 6-9 months. • Multiple drugs are needed because of resistance development issues. • Compliance is a big issue in TB therapy. • DOT (directly observed therapy) has helped TB treatment effectiveness • Most TB drugs are given orally.
Treatment of TB for HIV-Negative Persons • Include four drugs in initial regimen • Isoniazid (INH) • Rifampin (RIF) • Pyrazinamide (PZA) • Ethambutol (EMB) or streptomycin (SM) • Adjust regimen when drug susceptibility results are known
TB and HIV • An estimated 2 billion out of the world population of 6 billion have TB. • Each year there are 9 million new cases of TB in the world, and 2 million TB deaths. • An estimated 33 million people in the world are HIV positive. • Annual risk of TB disease with HIV is 10% per year • TB patients with HIV have a higher mortality
Drug Resistant TB • There are an estimated 500,000 multi-drug resistant (MDR) cases of TB in the world per year. • 2-10 % of MDR cases are extensively drug resistant (XDR) TB. • Of the recent HIV positive MDR TB patients, 80% (of 200) died within 4-19 weeks
Multidrug-Resistant Tuberculosis (MDRTB) • Seen especially in China, Russia, India, Estonia • Resistant to INH and Rifampin, the two core TB drugs • Cure rate 60% • Similar to per-chemotherapy era
MDRTB: Recent Outbreaks • Large numbers of Patients • Nosocomial transmission • HIV co-infection – 80% • High mortality
US MDR TB outbreaks • Inpatient or outpatient visits on an HIV ward were a major risk factor for MDR TB in Miami • 8.7% of 472 patients in an HIV dental clinic in NYC developed culture positive MDR TB • A number of nurses and doctors acquired MDR TB in the line of duty
XDR TB • Definition: TB resistant to INH, rifampin, quinolones and an injectable second line agent • Causes higher death rate than susceptible TB • A worldwide problem – especially in Africa • Amplified by HIV
XDR TB cases • 49 cases in the US up to 2006 • Increasing in incidence • Large outbreak in Africa in 2006 (52 of 53 died at a median of 16 days)
Treatment of MDR and XDR TB • Treat with 4-7 drugs to which the organism is sensitive for 18-24 months • Second line drugs are more toxic and less effective than INH and rifampin • Mortality is higher for MDR and XDR TB.
House panel review of traveling TB patient incident • The patient flew against medical advice to Paris on May 12, 2007 (with probable MDR TB) • On May 21, tests reported XDR TB. • On May 22, the CDC contacted the patient in Rome and told him not to travel • The patient and his wife changed their itinerary to elude public health authorities, and took several flights in Europe, and then flew from Prague to Montreal. • He re-entered the US, and a US Customs official let him through even though there was an order to not let him into the country. • Hundreds of airline passengers were tracked down.
House panel review of traveling TB patient incident: conclusions • The government should have used more aggressive measures to restrict the patient • The Customs and Border patrol's letting the patient into the US was an "egregious failure" • It took several hours for DHS to get the patient on the "no fly" list because he was not a terrorist • The CDC should have informed the WHO about the patient immediately, not 2 days later
Public Health and Welfare: Regulations to control communicable diseases • The government may quarantine (exposed persons) or isolate (infected patients) to "prevent the introduction, transmission or spread of communicable diseases". This includes "apprehension and detention" of individuals. • The Public Health Service Act authorizes DHHS to enact this provision (through the CDC) • Quarantinable diseases include diphtheria, TB, plague, smallpox, yellow fever, VHF, SARS, avian influenza. • State authority for isolation and quarantine is variable.
TB and air travel "Health officials are trying to track down 44 people who sat near a woman with MDR TB aboard an airliner from India to the US". January 2008, Reuters Health
TB and Air Travel (WHO, 2006) • Commercial jets built after the late 1980s recirculate cabin air, HEPA filter it, and blend it with outside air. • When the engine is running, the air is drawn from the compressor stages of the engines, enters the cabin from overhead, and exits near the floor. • While cruising, aircraft provide 20 air exchanges per hour. • In case of ground delays for more than 30 minutes the ventilation system should be operating. • TB transmission has only been documented on flights of 8 hours or more. • Most transmission occurs to persons in the same row, or 2 rows ahead or behind, the patient. SARS, and influenza, raise the question of wider spread. • TB patients should not travel until they are on therapy for 2 weeks. • MDR TB and XDR TB patients should not travel (until declared non-infectious).
TB and Air Travel (WHO, 2006) • Countries may require medical examination of arriving or departing passengers (or deny them entry). • Officers in command of aircraft are required to report any cases of illness indicative of a public health hazard on board. • Officers in command of aircraft may legally deny boarding to a person if they have a valid concern that they pose a health threat. • Physicians who are aware that an infectious TB patient is flying should inform public health. • Airlines have a system in place to reach passengers, and should cooperate with health authorities to reach them. However, the responsibility for contacting exposed passengers rests with public health authorities.