R. L. (Bob) Cowie, Health Research & Innovation Centre -- Case Report MDR Pulmonary TB

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In 20072010, 80 countries and 8 territories
reported surveillance data. MDR-TB among new and
previously treated cases was highest in the
Russian Federation (Murmansk oblast, 28.9) and
the Republic of Moldova (65.1), respectively. In
three former Soviet Union countries and South
Africa, more than 10 of the cases of MDR-TB were
extensively drug-resistant. Globally, in 1994 to
2010 multidrug resistance was observed in 3.4
(95 confidence interval, CI 1.95.0) of all new
TB cases and in 19.8 (95 CI 14.425.1) of
previously treated TB cases. No overall
associations between MDR-TB and HIV infection
(odds ratio, OR 1.4 95 CI 0.73.0) or sex
(OR 1.1 95 CI 0.81.4) were found. Between
1994 and 2010, MDR-TB rates in the general
population increased in Botswana, Peru, the
Republic of Korea and declined in Estonia, Latvia
and the United States of America.
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In 20072010, 80 countries and 8 territories
reported surveillance data. MDR-TB among new and
previously treated cases was highest in the
Russian Federation (Murmansk oblast, 28.9) and
the Republic of Moldova (65.1), respectively. In
three former Soviet Union countries and South
Africa, more than 10 of the cases of MDR-TB were
extensively drug-resistant. Globally, in 1994 to
2010 multidrug resistance was observed in 3.4
(95 confidence interval, CI 1.95.0) of all new
TB cases and in 19.8 (95 CI 14.425.1) of
previously treated TB cases. No overall
associations between MDR-TB and HIV infection
(odds ratio, OR 1.4 95 CI 0.73.0) or sex
(OR 1.1 95 CI 0.81.4) were found. Between
1994 and 2010, MDR-TB rates in the general
population increased in Botswana, Peru, the
Republic of Korea and declined in Estonia, Latvia
and the United States of America.
Zignol. Bull World Health Organ 201290111119
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Case Report MDR Pulmonary TB
56 year old man from Eritrea who was considered
to have inactive tuberculosis at the time of
immigration but for some reason was referred
urgently by immigration on his arrival in Canada.
Of course, Immigration Canada did not get it
right and gave him the wrong contact details for
Tuberculosis Service. He and his family were
very strongly motivated and persisted with
inquiries. One month later, one of his daughters
traced TB Services she did better than we did
as the address which Immigration Canada had given
us was incorrect and we were still trying!
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Case Report MDR Pulmonary TB (contin)
For the record all immigrants to Canada of 11
years of age and older as well as all those of
any age with a history of tuberculosis must have
a chest x-ray. If the x-ray is in any way
abnormal, they must be shown to not have active
tuberculosis before being allowed to come to
Canada. Those with abnormal x-rays are then
required to report to a designated centre to be
further evaluated for tuberculosis. All
immigrants sign a form to indicate that they are
aware of this but many do not understand what
they are signing and in most cases Immigration
does not tell them where they should report.
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Case Report MDR Pulmonary TB (contin)
Our patient was seen at the tuberculosis clinic
and gave a history of having twice before been
treated for tuberculosis. A sputum was sent
which was smear positive. Because of his
treatment history, he was started on treatment
with rifampin, isoniazid, ethambutol,
pyrazinamide, levofloxacin and amikacin. The
decision to add levofloxacin and amikacin was
based upon the likelihood that he had resistant,
if not multidrug resistant tuberculosis.
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Case Report MDR Pulmonary TB (contin)
He had been on treatment with R, H, Eb, Z,
Levo and Amikacin since 5 January 2011 After
receiving the sensitivity results, treatment was
changed to pyrazinamide, levofloxacin, amikacin
and ethionamide. He complained of joint pains
and of severe nausea and some vomiting and the
pyrazinamide, was stopped with resolution of the
symptoms, and cycloserine commenced. His sputum
cultures were negative by April 2011 and have
remained negative. Amikacin had to be stopped
after 6 months because of dizziness and
increasing deafness
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Case Report MDR Pulmonary TB (contin)
Plans are advanced for him to have his right lung
removed
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Case Report MDR Pulmonary TB (contin)
CONTACT TRACING
His household contacts included his wife, 3
teenagers and 5 young adults. All had positive
tuberculin skin tests His son-in-law lived in
another house but had been invaluable in meeting
the family when they arrived and transporting
them around Calgary, including bringing the
father to TB Clinic His son-in-law had a
transplanted kidney.
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Case Report MDR Pulmonary TB (contin)
CONTACT TRACING
What would you have done about his household
contacts and his immunocompromised son-in-law?
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Case Report MDR Pulmonary TB (contin)
CONTACT TRACING
What would you have done about his household
contacts and his immunocompromised son-in-law? We
examined all of his contacts and all were well
with no features to suggest disease. We elected
to follow their progress with the exception of
the son-in-law who had a positive TST and IGRA
and was given a 6 month course of levofloxacin.
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MDR TB

• The attention given to MDR-TB in recent years has
  not resulted in publications on preventive
  treatment for contacts of MDR-TB patients. The
  available evidence is not sufficient to support
  or reject preventive treatment. Furthermore, the
  combined available evidence is of very low
  quality.
• van der Werf, M. J IJTLD 201216288-296

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Groups of Drugs to Treat MDR TB
WHO Treatment of TB Guidelines 4e 2010
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Groups of Drugs to Treat MDR TB
WHO Treatment of TB Guidelines 4e 2010
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The Cost of Treating MDR TB
the cost of treatment varied from 3401 to
195 078, depending on the region and model of
care. The cost per DALY averted was lower than
GDP per capita in all 14 WHO sub-regions
considered, with better cost effectiveness for
outpatient versus inpatient models of
care. Unless there is strong evidence that
hospitalization is necessary to achieve high
rates of adherence to treatment, patients with
MDR-TB should be treated using mainly ambulatory
care. Fitzpatrick C, Floyd K (WHO).
Pharmacoeconomics 201230(1)63-80.
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Rapid Tests To Detect MDR TB The available rapid
tests to detect MDR TB are based on the detection
of rifampin resistance on direct specimens.
Several tests are available of which two are
favoured for use in Canada. INNO-LiPA Rif.TB test
Xpert MTB/RIF Both tests have high
sensitivity and specificity
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Rapid Tests To Detect MDR TB The rapid MDR (R-
resistance) tests are more problematic in a low
prevalence area such as Canada. Firstly it may
not be cost-effective to do these tests
routinely In addition, there is a significant
risk of false positive rifampin resistant
results And the risk that those with R resistance
will be INH susceptible and therefore not MDR may
be as high as 40 in low prevalence countries
Smith IJTLD 201216203
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Kurbatova IJTLD 2012 16(3)355357
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Late Breaking News
TB Alliance has announced a new treatment regimen
for MDR which they will test over 8 weeks The
regimen includes a nitroimidazoxazine, PA-824,
with moxifloxacin and pyrazinamide. PA-824 has a
low MIC and has been shown to be effective
against both susceptible and MDR tubercle bacilli
and against dormant and actively replicating
bacilli We must wonder how long it will take for
bad programs to create resistance to the new
drugs
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CONCLUSION
MDR is an increasing problem world-wide and
countries such as Canada who accept a large
number of immigrants from high incidence TB
countries must expect to see increasing numbers
of patients with MDR TB. In general, we have
limited experience with these cases and need to
familiarise ourselves with the international
guidelines for their management. The case
presented here gives some indication of how
complex the treatment is and the need to become
familiar with the toxic second-line drugs