TB and Drug Resistant TB Case Studies

TB TB andand

Drug Resistant TBDrug Resistant TBCase StudiesCase Studies

Philip W. Smith, MDPhilip W. Smith, MDChief, Infectious DiseasesChief, Infectious Diseases

University of Nebraska Medical CanterUniversity of Nebraska Medical Canter

Reported TB CasesUnited States, 1953 - 1998

Year

10,000

20,000

*

*

30,000

50,000

70,000

100,000

Case

s(L

og

Sca

le)

*Change in case definition

53 60 70 80 90 98

TB ResurgenceTB ResurgenceIncreased number of immigrants from Increased number of immigrants from countries with many cases of TBcountries with many cases of TB

Increased poverty, injection Increased poverty, injection drug use, and homelessdrug use, and homeless

Poor compliance with Poor compliance with treatment regimenstreatment regimens

HIV / AIDS Epidemic

Number of TB Cases inNumber of TB Cases inU.S.-born vs. Foreign-born Persons U.S.-born vs. Foreign-born Persons

United States, 1993–2005*United States, 1993–2005*

0

5000

10000

15000

20000

1993 1995 1997 1999 2001 2003 2005

U.S.-born Foreign-born

No

. o

f C

ases

*Updated as of March 29, 2006.

TuberculosisTuberculosis

Mycobacterium tuberculosisMycobacterium tuberculosis

Humans main reservoirHumans main reservoir

Inhalation of droplet nucleiInhalation of droplet nuclei

Most infected without diseaseMost infected without disease

5-15% develop disease 5-15% develop disease

Greatest risk first two years Greatest risk first two years

Findings of Pulmonary TB

CoughFeverWeight lossHemoptysisNight sweatsChest pain

X ray shows:– Infiltrate– Cavity– Upper lobe location

Transmission of Transmission of M. tuberculosis M. tuberculosis

Spread by airborne route; droplet nucleiSpread by airborne route; droplet nuclei

Transmission affected byTransmission affected by– Infectiousness of patientInfectiousness of patient– Environmental conditionsEnvironmental conditions– Duration of exposureDuration of exposure

Most exposed persons do not become Most exposed persons do not become infectedinfected

Administering the TSTAdministering the TSTInject 0.1 mL PPD Inject 0.1 mL PPD intradermallyintradermallyShould produce wheal of Should produce wheal of 6–10 mm6–10 mmDo not recap, bend, Do not recap, bend, break, remove needles break, remove needles from syringesfrom syringesFollow standard IC Follow standard IC precautionsprecautions

Reading the Tuberculin Skin Test

•Read reaction 48-72 hours after injection

•Measure only induration

•Record reaction in millimeters

Interpreting TST Result (2)Interpreting TST Result (2)

Different cut points used depending onDifferent cut points used depending onPatient’s risk for having LTBIPatient’s risk for having LTBI

Size of indurationSize of induration

>>5 mm5 mm highest riskhighest risk

>>10 mm 10 mm other risk factorsother risk factors

>>15 mm15 mm no known risk factorsno known risk factors

CXR

AFB smear

AFB (shown in red) are tubercle bacilli

CulturesCultures

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 TBDrug 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, Of the recent HIV positive MDR TB patients, 80% (of 200) died within 4-19 weeks80% (of 200) died within 4-19 weeks

Multidrug-Resistant Tuberculosis Multidrug-Resistant Tuberculosis (MDRTB)(MDRTB)

Seen especially in China, Russia, Seen especially in China, Russia, India, EstoniaIndia, Estonia

Resistant to INH and Rifampin, the Resistant to INH and Rifampin, the two core TB drugs two core TB drugs

Cure rate 60%Cure rate 60%

Similar to per-chemotherapy eraSimilar to per-chemotherapy era

MDRTB: Recent OutbreaksMDRTB: Recent Outbreaks

Large numbers of Patients Large numbers of Patients

Nosocomial transmission Nosocomial transmission

HIV co-infection – 80%HIV co-infection – 80%

High mortalityHigh 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 TBXDR TB

DefinitionDefinition: TB resistant to INH, rifampin, : TB resistant to INH, rifampin, quinolones and an injectable second quinolones and an injectable second line agentline agent

Causes higher death rate than Causes higher death rate than susceptible TBsusceptible TB

A worldwide problem – especially in A worldwide problem – especially in AfricaAfrica

Amplified by HIVAmplified 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 diseasesThe 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.