2/9/2012
1
Tuberculosis Local and Global Perspectives
MUSC February 7, 2012
Eric Brenner, MDBureau of Disease Control
SC DHEC
Dept of Epidemiology and BiostatisticsUSC School of Public Health
Columbia, SC
A case of TB from the 1950s ‐ IA State Sanatorium Hospitalization
• Young woman ~30 y.o. from Coastal SC
• Pulmonary TB, Far Advanced, Bilateral
• Admitted: July 1953
• Discharged: November 1959
• Length of stay: 6 years + 4 months
• Discharged for “disciplinary reasons” !
A case of TB from the 1950s II ‐ Treatment
• Bed Rest (1953‐1959)
• Chemotherapy (various courses 1953‐1959)
• Surgery– Pneumoperitoneum November 1953‐August 1955
– Thoracoplasty, 1st stage right: January 1956
– Thoracoplasty, 2nd stage right, February 1956
– Pulmonary lobectomy, RLL, October 1958
A case of TB from the 1950s III ‐ Discharge
• Discharge Diagnoses:
– Pulmonary TB, far advanced, bilateral
– Pregnancy (two occasions)
• delivered September 1956 and March 1958
• Discharge Medications:
– INH 300 mg qd and PAS 12 gm qd indefinitely (!)
• Other instructions:
– X‐ray and sputum q 3‐4 months
– Do no work
Schema of a typical modern case of TB
• January ‐March: progressive cough, night sweats, weight loss, fatigue. Several MD visits => considered “bronchitis”, “walking pneumonia”, “pertussis” etc. Various antibiotics have no effect.
• April 1: Referred to Infectious Disease specialist who finally “thinks TB” => presumptive Dx with 3 AFB positive smears (Dx later confirmed by +cultures)=> treatment begins April 4
• Treatment: daily for 2 weeks (3 days in hospital + 11 days) at home; then twice‐weekly for 24 weeks directly supervised at home, work, or in pool‐hall by a public health nurse (PHN); sucessful treatment (62 doses) ends October 4.
• PHN also completed contact investigation (home, work, and social contacts); identified infected but asymptomatic persons who were treated for latent TB infection (LTBI).
Outcomes of TB According to TB Program Setting
0%10%20%30%40%50%60%70%80%90%
100%
No Program Poor Program Good Program
Chronic
Cure
Die
?
2/9/2012
2
Robert Koch (1843‐1910)Discover of the “tubercle bacillus” in 1882
Some Landmarks in the History of Tuberculosis
• 1882 Koch discovers the tubercle bacillus
• 1890 Koch develops tuberculin (initially as Rx for TB?)
• 1895 Roengten discovers x‐rays
• 1900‐1960s Sanatoria as TB hospitals (bed rest + some surgery!)
• 1921 BCG vaccine (Bacillus of Calmette & Guerin = attenuted M. bovis)
• 1944 Streptomycin first used to treat a patient
• 1949 PAS (para‐aminosalycylic acid)
• 1952 Isoniazid (Rx often lasts 18‐24 months)
• 1954 Pyrazinamide
• 1962 Ethambutol
• 1963 Rifampin
• 1970s Rx shortened to 9 months for most pts
• 1980s Rx shortened to 6 months for most pts
• 1990s Challenges => MDRTB, TB+HIV=double trouble; Full magnitude of Global TB epidemic finally appreciated
Some Mycobacterial Species of Medical Importance
• M. TB complex
– M. tuberculosis
– M. bovis (including BCG)
– M. africanum
• Non tuberculous mycobacteria (NTM)
– M. avium‐intracellular (M. intracelluare, MAI, MAC)
– M. kansassi
– M. fortuitum
– M. chelonei
– (and several dozen other species)
• M. leprae [agent of Leprosy or “Hansen’s Disease]
A normal PA x‐ray of the chest
2/9/2012
3
Mycobacteriology Laboratory ‐ IIIAFB Smears
• Detects presence of mycobacteria (and occasionally other uncommon pathogens as well ‐ e.g. Nocardia)
• Cannot distinguish M. TB from NTM.
• Clue to possible diagnosis AND to potential infectiousness of patient.
• Always interpret in context of all other findings.
Mycobacteriology Laboratory ‐ IVMore Positive AFB Smears (*)
(*) Again with traditional Ziehl‐Neelsen staining which most hospitals can do
Mycobacteriology Laboratory ‐ VFluorochrome Method for Mycobacterial Smears
• More sensitive than traditional ZN staining
• Uses auramine‐rhodamine stain
• Requires special equipment which smaller hospitals will not have
M. Tuberculosis colonies growing on agar in the laboratory
Schema of the Pathogenesis of Tuberculosis
Lymphatics => systemic circulation via the thoracic duct
Dissemination via circulation to distant sites including (i) apex of lungs; (ii) kidneys, (iii) bone, (iv) brain, (v) multiple other sites. Potential for disease to occur in 5‐10% of infected persons; months, years, decades later.
Spread via pulmonary lymphatics
Site of initial infection often peripheral (sub‐pleural)
Typical apical cavitarydisease seen in many patients who have TB from late reactivation of Latent TB Infection (LTBI)
Hilar lymph nodes (hilar adenopathy)
2/9/2012
4
Natural History of Tuberculosis (Schema)
Not Infected Infected +
No disease, but LTBI
Disease “soon” [within 1‐2 yrs]
Still no disease, but possible lifelong LTBI
Disease “anytime later in life” [reactivation of LTBI)
100%
5%
95%
5%
90%
Caution !! Co‐infection with HIV totally upsets this schema!Instead of having a 10% lifetime risk of developing TB disease persons co‐infected with HIV may have a risk as high as 10% per year!!!!
Back to a bit of TB History!
In 1914, $10,000 was set aside by the legislature to establish the South Carolina State Sanatorium. The State Sanatorium opened in 1915 as a tent facility and over time, progressed to wooden buildings or cottages. TB Camps were established all over SC –Hopewell in Greenville, Camp Alice in Sumter, Pinehaven in Charleston, Marion County Camp
A Cottage at the Ridgewood SanatoriumNote the windows all around the building and the swings & chairs in the yard for the “fresh air cure”
Pavilion at the TB San
Reminder of the not‐so‐distant pastAn imposing Sanatorium TB hosptial Note extensive sun‐porches = Solariums Mont‐Joli (Quebec; 1939)
2/9/2012
5
State Park Health Center opened in 1938
“Sun treatment” for TB early in the early XXth. century
This picture shows mass screening in the United States. These projects started in the 1930s. Mass screening with conventional equipment was impractical, so special devices were developed. Mobile vans equipped with photofluorographic X‐ray units allowed countries around the world to mass screen their populations...
Visting patients in the TB sanatorium…. (is that why they call him Santa?)
Patients taking the air at the Ninette Tuberculosis Sanitorium, Manitoba[www.umanitoba.ca/faculties/medicine/units/history/mbhist/ninnimag.html]
South Carolina Board of Health
A TB patient at the sanatorium getting an X‐ray completed.
2/9/2012
6
South Carolina Board of Health
X‐rays were less expensive, easier to complete and used more & more both in and outside the Sanatorium setting.
Cut‐out drawing of a mobile X‐ray Van
State Board of Health hired 7 public health nurses; Ruth Dodd and Helen Fenton were the first TB public health nurses in South
Carolina. They were to teach the TB patients how to take care of themselves and prevent others from getting TB
Modern TB Chemotherapy
2/9/2012
7
In concert with ALASC, DHEC developed and started the Enablers and Incentives Program. The funding was provided by the ALASC through a trust fund and still functions today.
2/9/2012
8
Immigration Routes for the First Americanswww.roebuckclasses.com/201/conquest/nativehistoryoutline.htm
http://year8exploration.wikispaces.com/Victoria
Columbus’ Four Voyages to the New World: 1492, 1493, 1498 & 1502 First (2003) US Cow with Bovine Spongioform Encephalopathy (BSE) [ “Mad Cow Disease”] had been imported from Canada in 2001
“Swine flu” (H1N1 of 2009) imported from Mexico
Another old Question about disease importation:
Was there Tuberculosis in the New World before the arrival of Columbus and other Europeans?
2/9/2012
9
NYT March 15, 1994
But…. On a more immediate and practical note, how about importations of TB into the USA right now in the 21st Century?
Case of TB Imported from India ‐ 1
• 29 yo woman arrives SC Aug 2004
• part of group of teachers from India with contracts to teach science in underserved rural SC high schools
• Contracting agency did not know of her two previous episodes of pulmonary TB (had self‐administered therapy!?)
• TB relapses Summer 2005 => smear+ & culture+
• At first just one of ~ 200 SC TB cases for the year…. but…
• Drug susceptibilities: => R to INH, Rif & PZA
• Rx then proceeds with Emb, Cys, Cap, Lev, Mox, Rfb
• Complex course (e.g. drug intolerance, other systemic diseases) requires several regimen modifications
• Eventual good treatment outcome: completed teaching contract. Now studying nursing in Georgia
Case of TB Imported from India ‐ 2 Case of TB Imported from India – 3Contact Investigation
• Spouse and sister have +TSTs
– PEP with Rx with Rifabutin
• All co‐teachers in the HS now tested.
• Only one student patient had taught had a positive skin test. Felt had likely been infected before.
– PEP with Isoniazid
• Complex, this case only one of over 5,000 foreign born TB cases seen in the USA each year
2/9/2012
10
What overview then of Tuberculosis in the USA and its Relation to “Importation”
Reported TB Cases United States, 1982–2010*
*Updated as of July 21, 2011
0
5,000
10,000
15,000
20,000
25,000
30,000
No. o
f Cases
Year
TB Case Rates* by Age Group United States, 1993–2010
* Updated as of July 21, 2011
0.0
5.0
10.0
15.0
20.0
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
2008
2009
2010
0‐ 14 15 ‐ 24 25 ‐ 44 45‐65 >65
Cases per 100,000
TB Case Rates by Age Group and Sex, United States, 2010
0.0
1.0
2.0
3.0
4.0
5.0
6.0
7.0
8.0
9.0
Under 5 5 ‐ 14 15 ‐ 24 24 ‐ 44 45‐64 ≥65
Male Female
Cases per 100,000
Number of TB Cases inU.S.-born vs. Foreign-born Persons
United States, 1993–2010*
0
5,000
10,000
15,000
20,000
U.S.‐born Foreign‐born
*Updated as of July 21, 2011
No. of Cases
>50%
25%–49%<25%
2000 2010
DC
*Updated as of July 21, 2011
Percentage of TB Cases Among Foreign‐born Persons, United States*
DC
2/9/2012
11
Primary Isoniazid Resistance in U.S.‐born vs. Foreign‐born Persons
United States, 1993 – 2010*
*Updated as of July 21, 2011
Note: Based on initial isolates from persons with no prior history of TB.
0
2
4
6
8
10
12
14
199319941995199619971998199920002001200220032004200520062007200820092010
U.S.‐born Foreign‐born
% Resistant
XDR TB Case Count Defined on Initial DST* by Year, 1993 – 2010**
* Drug susceptibility test** Updated as of July 21, 2011Note: Extensively drug‐resistant TB (XDR TB) is defined as resistance to isoniazid and rifampin, plus resistance to any fluoroquinolone and at least one of three injectable second‐line anti‐TB drugs
0
2
4
6
8
10
12
199319941995199619971998199920002001200220032004200520062007200820092010
Case Count
Year of Diagnosis
Estimated HIV Coinfection in Persons Reported with TB, United States, 1993 – 2010*
*Updated as of July 21, 2011
Note: Minimum estimates based on reported HIV‐positive status among all TB cases in the age group
0
5
10
15
20
25
30
199319941995199619971998199920002001200220032004200520062007200820092010
Aged 25‐44 All Ages
% Coinfection
Mode of Treatment Administration in Persons Reported with TBUnited States, 1993 – 2008*
*Updated as of July 21, 2011. Data available through 2008 only.**Percentage of total cases in persons alive at diagnosis, with an initial regimen of one or more drugs prescribed, and excluding cases with unknown mode of treatment administration.Directly observed therapy (DOT); Self‐administered therapy (SA)
0
20
40
60
80
100
1993199419951996199719981999200020012002200320042005200620072008
DOT only DOT + SA SA only
Percentage**
Completion of TB TherapyUnited States, 1993 – 2008*
* Updated as of July 21, 2011. Data available through 2008 only.Note: Includes persons alive at diagnosis, with initial drug regimen of one or more drugs prescribed, who did not die during therapy. Excludes persons with initial isolate rifampin resistant, or patient with meningeal disease, or pediatric patient (aged<15) with miliary disease or positive blood culture.
0
10
20
30
40
50
60
70
80
90
100
1993199419951996199719981999200020012002200320042005200620072008
Completed Completed in 1 year or less
Percentage
And… how is it that we (or CDC) even know all this about TB in the foreign born?
2/9/2012
12
Global Perspectives!
Geneva, Switzerland The “Pont du Mont Blanc” where the Lake of Geneva empties into the Rhone River
The old “League of Nations” Building (now part of UN) HQ of the World Health Organization
2/9/2012
13
The Six WHO Regions
Flashback…. to the eradication of smallpox.
2/9/2012
14
Images of SmallpoxSmallpox Day 8
2/9/2012
15
Control Reduction of disease incidence, prevalence, morbidity, mortality, and disability to a locally acceptable level.
Elimination Reduction of infection and disease to zero in a defined area. Surveillance crucial. Continued efforts required.
Eradication Permanent reduction of worldwide incidence to zero as a result of deliberate interventions. Surveillance crucial. Continued efforts may not be required.
Destruction Destruction of all isolates of microbial agent.
“Stages” in the disease control wars
2/9/2012
16
Elimination of TB in the USA !?
• What would the term “elimination mean?
• Is “elimination” an appropriate goal or not…. and, if so:
• For what date and for what sub‐populations should “elimination” be targetted?
• Should DTBE have its named changed back to the DTBC?
Thank you!
Discussion …. ?