Transcript Slide 1

Drug Resistant Tuberculosis: An Overview
July 14, 2014, Pokhara, Nepal
Dr. Sharat Chandra Verma
Chief Consultant Chest Physician
National TB Centre
Nepal
/fli6«o Ifo/f]u sfo{qmd
National Tuberculosis Center
Some definitions
• Multi-Drug Resistant (MDR) TB: MDR-TB is defined
as TB caused by bacteria resistance to isoniazid and
rifampicin, with or without resistance to other firstline drugs (FLD).
• Extensive Drug Resistant (XDR) TB: XDR-TB is
caused by bacteria that are resistant to rifampicin
and isoniazid as well as resistant to any one of the
fluoroquinolones (e.g. ofloxacin and moxifloxacin)
and to at least one of the injectable second-line
drugs (capreomycin, kanamycin or amikacin).
/fli6«o Ifo/f]u sfo{qmd
National Tuberculosis Center
Why is MDR-TB a problem?
• Possibility of resistance to all major anti-TB
drugs
• Treatable, but requires extensive therapy: up
to 2 yrs of treatment
• Expensive
• Treatment could be toxic to patients
/fli6«o Ifo/f]u sfo{qmd
National Tuberculosis Center
How is DR-TB transmitted?
• TB bacilli with different levels of resistance
spread in the same way and with the same
risk of infection as fully drug susceptible
strains.
– Person-to-person through inhalation of
droplet nucleii
– Infected person usually coughs or sneezes
and projected infected droplet nucleii into
the air
/fli6«o Ifo/f]u sfo{qmd
National Tuberculosis Center
Pathogenesis of
Drug Resistance
/fli6«o Ifo/f]u sfo{qmd
National Tuberculosis Center
Frequency of Resistance Mutations
INH = 1 in 106
RIF = 1 in 108
EMB = 1 in 106
Strep = 1 in 106
INH + RIF =
1 in 1014
/fli6«o Ifo/f]u sfo{qmd
National Tuberculosis Center
Development of Drug Resistance
Multiple Drugs vs. Monotherapy
INH
RIF
PZA
1
2
I
R
P
INH
I
I
I
I
I
3
I
/fli6«o Ifo/f]u sfo{qmd
I = INH resistant, R = RIF resistant, P = PZA resistant
National Tuberculosis Center
Development of Drug Resistance (2)
Further acquired resistance after single drug added
I
I
I
I
I
I
I
INH
I
I
I
INH
RIF
IR
I
I
I
I
I
I
I
I
IP
I
I
IR
IR IR
IR
IR IR IR
IRP
IR IR
IR
IR
IR
IR
/fli6«o Ifo/f]u sfo{qmd
I = INH resistant, R = RIF resistant, P = PZA resistant
National Tuberculosis Center
Unintended Monotherapy and Resistance
Months of Rx
0
5
7
9
Smear
+
+
+
+
Culture
+
+
+
+
INH
R*
R
R
R
RIF
S*
R
R
R
EMB
S*
S
S
R
INH
RIF
EMB
Susceptibility
/fli6«o Ifo/f]u sfo{qmd
* Results
not Tuberculosis
known to clinician
National
Center
Factors that Lead to Drug Resistance
Causes of inadequate treatment:
• Patient-related factors
• Healthcare provider-related factors
• Healthcare system-related factors
/fli6«o Ifo/f]u sfo{qmd
National Tuberculosis Center
Factors that Lead to Drug Resistance
Patient-related factors:
• Non-adherence, default
• Malabsorption of drugs
• Adverse drug reactions
• Lack of information, transportation, money
• Social barriers to treatment adherence
• Substance dependency disorders/fli6«o Ifo/f]u sfo{qmd
National Tuberculosis Center
Factors that Lead to Drug Resistance
Healthcare provider-related factors:
• Inadequate initial treatment regimen: Wrong
combination or doses, guideline noncompliance
• Treatment “in the dark” for retreatment cases:
no drug susceptibility testing available, or results
delayed
• Clinical errors: Adding a single drug to a failing
regimen
• Lack of proper monitoring
• Lack of proper provider awareness /fli6«o Ifo/f]u sfo{qmd
National Tuberculosis Center
Factors that Lead to Drug Resistance
Healthcare programme-related factors:
• Unavailability of drugs (stock-outs or delivery
disruptions)
• Poor drug quality, poor storage conditions
• Poorly organized or under-funded TB-control
programmes
• Inappropriate or no guidelines
• Lack of appropriate or timely laboratory testing
/fli6«o Ifo/f]u sfo{qmd
National Tuberculosis Center
Epidemiology
• In practice, MDR-TB develops either because
the person is infected initially with a:
– Drug-resistant strain (primary), or
– Susceptible strain that becomes resistant
(secondary)
/fli6«o Ifo/f]u sfo{qmd
National Tuberculosis Center
Epidemiology cont.
• Reasons for secondary resistance are
numerous and complex:
– Wrong drugs used in an improper way
– Failure to assess drug susceptibility patterns of the
organism
– A large bacterial load, especially in the case of
cavitation
– Poor adherence to the treatment regimen
/fli6«o Ifo/f]u sfo{qmd
National Tuberculosis Center
Epidemiology cont.
• TB (including MDR-TB) and HIV co-infections are relatively
common globally and each condition adversely affects the
other.
/fli6«o Ifo/f]u sfo{qmd
National Tuberculosis Center
MDR-TB notification and enrolment
MDR cases reported vs estimated among notified TB, 2012: WHO 2013
WHO Region
2012
Estimated
Reported
Ratio
38,000
18,129
48%
American
7,100
2,967
42%
East Med.
18,000
2,236
12%
European
74,000
36,708
50%
S-E Asian
90,000
19,202
21%
West Pacific
74,000
4,473
6%
African
Global
300,000
83,715
28%
/fli6«o Ifo/f]u sfo{qmd
National Tuberculosis Center
XDR-TB
• In 2006, the first reports of extensively drugresistant tuberculosis (XDR-TB) began to
appear.
• About 9.6% (8.1-11.2%) of MDR-TB cases in
countries with representative surveillance
data have XDR-TB. By October 2013, 92
countries had reported one or more XDR-TB
cases. (WHO Report 2013)
/fli6«o Ifo/f]u sfo{qmd
National Tuberculosis Center
Development of extensive drug resistance in
Multi-Drug resistant tuberculosis patients
• XDR-TB emerges like MDR-TB through
mismanagement of treatment.
• It is however believed that many cases of XDR
TB are never diagnosed due to a lack of
laboratory capacity to test for resistance to
second line drugs.
/fli6«o Ifo/f]u sfo{qmd
National Tuberculosis Center
Clinical Manifestations
• MDR-TB are not clinically distinguishable from
drug-susceptible TB at the outset.
• Signs, symptoms, and radiological findings are
similar initially to drug-susceptible TB.
/fli6«o Ifo/f]u sfo{qmd
National Tuberculosis Center
Reasons to suspect drug resistance are:
• A history of previously treated TB in a person presenting with
active TB
• High community rates of drug resistant TB
• Positive HIV status
• High likelihood of exposure to nosocomial, prison or
community sources of MDR-TB
• The infected person is from a country with a high MDR-TB
rates
• Contacts with persons with MDR-TB
• Infected person has received inadequate treatment regimens
for >2 weeks
• Smears or cultures remain positive despite 2 months of
treatment for TB
/fli6«o Ifo/f]u sfo{qmd
National Tuberculosis Center
Symptoms of Dr-TB is no different
from ordinary TB
• Cough (usually
productive and maybe
bloody)
• Low-grade fever
• Sweating
• Chills at night
• Fatigue
• Malaise
• Anorexia
• Shortness of breath
• Weight loss
• Dull, aching chest pain
or tightness
• Symptoms of
extrapulmonary TB
depend on the organ
system involved but
may include systemic
symptoms.
/fli6«o Ifo/f]u sfo{qmd
National Tuberculosis Center
Early identification and prompt
treatment of DR-TB
• Prevents the spread of disease,
• Helps stop development of further
amplification of resistance,
• Reduces the progression to permanent lung
damage, and
• Results in higher cure rates.
/fli6«o Ifo/f]u sfo{qmd
National Tuberculosis Center
Thank You
/fli6«o Ifo/f]u sfo{qmd
National Tuberculosis Center