Download Drug-resistant TB

Multi-drug Resistant
Tuberculosis
MDR-TB
Leah Erenrich
Advisor: Dr. Rapp
MDR-TB Defined
• Multi-drug resistant Tuberculosis is defined
as “strains of Mycobacterium tuberculosis
that are resistant to both isoniazid and
rifampin with or without resistance to other
drugs” (Blondal 2007).
• Second-line antibiotics => much more
expensive, more toxic, are difficult to
sterilize, and are much less effective
First line treatment
**MDR-TB**
Epidemiology
• Globally, the incidence of multi-drug
resistant tuberculosis is around 3.4%.
• China, India and the Russian Federation
are estimated to account for 62% of the
overall incidence of MDR-TB.
Epidemiology
• Some of the highest statistics of HIV and multidrug resistant tuberculosis co-infection are seen
in sub-Saharan Africa where HIV/AIDS
prevalence is so high.
• Currently, world wide MDR-TB mortality rates
are at about “40-60% depending on the country
of residence and access to immediate care”.
These rates are consistent with the rates of
untreated tuberculosis (Ducati et al. 2006).
M&M
• Morbidity and mortality rates in the United States
steadily declined over the years until the 1980’s
when a 2.6% annual increase in cases was
discovered.
• The sudden increase was attributed to,
“deterioration of the tuberculosis program
infrastructure, the HIV/AIDS epidemic, drugresistant tuberculosis, tuberculosis among
foreign-born persons, and an increase in
transmission, especially in congregate and
institutional settings” (Schneider et al. 2005).
Drug-Resistance-How it Happens
• When the bacilli are exposed to an antituberculosis medication, most are killed. If there
are some bacilli present that are resistant to that
particular antibiotic, they will mutate and multiply
freely. These random chromosomal mutations
may occur by nucleotide insertions, deletions, or
substitutions (Ducati et al. 2006).
• If the patient is given two or three antibiotics, this
inhibits the multiplication of resistant mutants
due to the unlikelihood that all of the bacilli
would be resistant to all three anti-tuberculosis
medications (Sharma et al. 2007).
Rifampin and Isoniazid
• Mycobacterium tuberculosis becomes
resistant to rifampin by an alteration of the
B-subunit of RNA polymerase, the rpoB
gene
• The genes involved in isoniazid resistance
are katG, inhA, ahpC, and oxyR
Causes of Drug Resistance
• “The most powerful predictor of the presence of MDR-TB is the
history of treatment of tuberculosis”. (Sharma 2006)
• inadequate treatment is received due to the installment of
inadequate programs having poor guidelines that use mono therapy
antibiotic treatment
• when the mono therapy doesn’t work, practitioners are adding only a
single drug to the regimen instead of two or three drugs
• poor supply or lack of quality of drugs
• lack appropriate storage for the drugs
• patient compliance in taking the prescribed medication
• failure of equipment, lack of laboratory support, and appropriate
facilities for things such as cultures and sensitivity testing
Presentation
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Sneezing
coughing
deep cough with bloody sputum
chest pain
Chills
unintended weight loss
slight fever
night sweats
loss of appetite
pain with breathing
Diagnosis
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History is IMPORTANT
Mantoux tuberculin skin test (TST)
chest radiograph
QuantiFERON-TB Gold test (QFT-G)
The presence of acid-fast bacilli on a sputum
smear may aid in the diagnosis of tuberculosis,
but it is not 100% diagnostic.
• The definitive diagnosis is made with a culture of
the smear.
• susceptibility testing by culture and sensitivity
Treatment
• “If the patient’s active-tuberculosis shows
resistance to isoniazid and rifampin, begin
treatment with a floroquinoline,
pyrazinamide, ethambutol, and an
injectable agent such as an
aminoglycoside (kanamycin, amikacin,
streptomycin), or the glyycopeptide,
capreomycin” (Nations 2006). Treatment
should continue for 18-24 months
Management
• DOTS
• DOTS-plus
• Vaccines
DOTS
• “Political commitment to effective TB control
• Case detection by sputum smear microscopy among
symptomatic people
• Standardized treatment regimen of 6-8 months of shortcourse chemotherapy with first-line anti-TB drugs,
administered under proper case management
conditions, including direct observation
• Uninterrupted supply of all essential anti-TB drugs
• Standardized recording and reporting system allowing
assessment of treatment results” (Frieden 2005)
DOTS-plus
• “Sustained political and administrative commitment
• Accurate, timely diagnosis through quality-assured culture and drug
susceptibility testing
• Uninterrupted supply of quality assured first and second-line drugs,
appropriate treatment strategies utilizing second-line drugs under
strict supervision
• Directly observed treatment
• Standardized recording and reporting system that enable
performance monitoring and evaluation of treatment outcome”
(www.who.int/gtb/policyrd/DOTSplus.htm)
• In a retrospective study assessing the treatment results in the
Latvian DOTS-plus strategy, data has shown itself to be promising.
There were 204 MDR-TB cohorts in this study, and of the 204, “66%
were cured, 7% died, 13% defaulted, and 14% did not respond to
treatment” (Sharma et al. 2007).
Vaccines
• BCG, the Bacille Calmette-Guerin vaccine
• over 100 vaccine candidates
• current BCG vaccine in a prime-boost
strategy
• BCG vaccine in combination with a new
vaccine candidate
Vaccine Candidates
• MVA-Ag85A
– The first tuberculosis vaccine candidate that
entered into a phase I trial in 2003 was
Ag85A, an “immuno-dominant protective
antigen from M. tuberculosis expressed in a
replication-deficient strain of vaccine virus
(MVA-Ag85A)”. (Ginsburg 2002)
• BCG prime/MVA-Ag85A
XDR-TB
• When Mycobacterium tuberculosis is
resistant to “at least 3 of the 6 classes of
second-line anti-tuberculosis drugs”, it is
identified as extensively drug-resistant
tuberculosis, XDR-TB (XDR-TB 2006).
XDR-TB
Conclusion
• MDR-TB is a problem!
• As PAs we must follow our appropriate
procedures for diagnosing, reporting, and
treating
• We can be effective globally with our time,
education, supporting research for
vaccines, etc.
Works Cited
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Blondal K. Barriers to reaching the targets for tuberculosis control: multi-drug resistant tuberculosis. Bull World Health Organ. 2007 May;
85(5): 387-90.
Brennan, MJ. Development of new tuberculosis vaccines: a global perspective on regulatory issues. Health in Action. 2007 Aug; 4 (8):
1299-1302.
Center for Disease Control. Trends in Tuberculosis---United States, 2005. MMWR Weekly. 2006 March [cited 2007 Sept]; 55(11):[7
pages]. Available from: http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5511a3.htm
Christensen, D. Another look at TB vaccine: Should the United States use BCG widely? Science News. 2000 Jun 18; 4(12): 23-35.
Ducati RG, Netto AR, Basso LA, Santos DS. The resumption of consumption – A review on tuberculosis. Rio de Janeiro. 2006 November;
101 (7); 697-714.
Extensively drug-resistant tuberculosis (XDR-TB): recommendations for prevention and control. Wkly Epidemiol Rec. 2006 Nov 10;
81(45): 430-2.
FitzGerald JM. Et al. Essentials of tuberculosis control for the practicing physician. Can Med Assoc J 1994; 150 (10): 1561-1571.
Frieden, TR. The DOTS strategy for controlling the global tuberculosis epidemic. Clin Chest Med. 2005 Jun; 26 (2) : 197-205.
Ginsberg, AM. What’s new in tuberculosis vaccines? Bulletin of the World Health Organization. 2002 80 (6): 483-488.
Johnson, MD, Decker, CF. Tuberculosis and HIV infection. Dis-Mon. 2006 Nov; 52 (11-12): 420-427.
Kidder, Tracy. Mountains Beyond Mountains. Random House Trade Paperbacks. August 31, 2004.
Martin, C. The dream of a vaccine against tuberculosis; new vaccines improving or replacing BCG? European Respiratory Journal. 2005;
26 (1): 162-167.
Nations, JA. Drug-resistant tuberculosis. Dis-Mon. 2006 Nov; 52 (11-12): 435-440.
Sampaio J. Stronger health systems to beat TB. Bull World Health Organ. 2007 May: 85(5):333.
Senior, K. Action needed now to prevent resistant tuberculosis. The Lancet Infectious Diseases. 2007 Aug; 7 (8) : 511.
Schneider, E. Epidemiology of tuberculosis in the United sSates. Clin Chest Med. 2005 Jun; 26(2) : 183-195.
Sharma SK, Mohan A. Multidrug-Resistant Tuberculosis: A Menace that Threatens to Destabilize Tuberculosis. Chest. 2006 Jul; 130 (1)
: 261-272.
Shiferaw G, Woldeamanuel Y, Gebeyehu M, Girmachew F, Demessie D, Lemma E. Evaluation of microscopic observation drug
susceptibility assay for detection of multidrug-resistant Mycobacterium tuberculosis. J Clin Microbiol. 2007 Apr: 45(4): 1093-7.
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