Download A Review of Zoonotic Tuberculosis at the Human-Livestock

Zoonotic Tuberculosis at the
Human-Livestock-Wildlife
Interface
Meghan Gibas
Colorado State University
College of Veterinary Medicine & Biomedical Science
Outline
• Background
• Rationale
▫ Systematic Literature Review
▫ Preliminary Field Data
• Conclusion/Implications
Tuberculosis in Humans
• TB in humans is primarily caused by
Mycobacterium tuberculosis (M. tb)
• TB is an infectious-contagious disease
and represents one of the leading causes
of death from an infectious disease
worldwide.
▫ 8.7 million new cases of TB in 2011
▫ 1.4 million deaths in 2011
(WHO Annual TB report, 2011)
(3,833 deaths/day)
Mycobacterium bovis (M. bovis)
• The main host of M. bovis
is cattle
• 128 out of 155 countries
reported the presence of M.
bovis infection and/or
clinical disease in their
cattle population between
2005 and 2008 (Michel et al, 2010)
• Most warm-blooded
vertebrates can be
infected.
including
humans
Transmission & Pathology of
M. bovis in Humans (Zoonotic TB)
▫ Orally (unpasteurized dairy products) or through inhalation
(Michel et al., 2010)
▫ Patients with extra-pulmonary disease had increased odds of
having M. bovis vs. M. tb (Hlavsa et al., 2008)
▫ M. bovis can be an important etiological agent for extra
pulmonary TB, especially in HIV-infected patients. (Cicero et al., 2009)
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M. bovis Resistant to PZA
• M. bovis is naturally resistant to pyrazinamide (PZA), a
critical component to effective short course TB treatment.
• Thus, patients with undiagnosed M. bovis are being
treated sub-optimally.
Challenges of Zoonotic TB
• Conditions in the developing world:
(Cosivi et al., 1998; Thoen et al., 2006).
▫
▫
▫
▫
Higher prevalence of bovine TB in livestock
Lack of milk pasteurization
Human immunodeficiency virus (HIV)
Close interaction between humans, livestock, and wildlife species
Challenges of Zoonotic TB
▫ 1.4% is the generally perceived estimate for the
proportion of human TB cases infected with M. bovis.
 Lack of targeted surveillance
▫ Scientific evidence indicates that the true risk of human
TB caused by M. bovis is under investigated/under
estimated/under reported.
(Cosivi et al., 1998; Kazwala et al., 2001; Ayele et al., 2004; Danker and Davis, 2005; Hlavsa et al., 2008; Thoen et al.; 2010;
de Kantor et al., 2010; Michel et al., 2010).
Research
questions
1) What is the range of risk estimates of M. bovis infection
(zoonotic TB) among humans diagnosed with TB?
- The risk of zoonotic TB was defined as the proportion of
human TB patients infected with M. bovis.
2) What are the key study design characteristics that may
contribute to the heterogeneity between different studies when
estimating the risk of zoonotic TB?
Key Study Characteristics
Range of risk estimates of M. bovis infection
• There is a large variation (a range of 0-45%) in the risk estimates of M.
bovis infection in human TB patients.
• 16 of the studies (26%) reported a >10% risk of M. bovis.
Results
•
53% of studies used culture
positive TB patients as patient
inclusion criteria.
•
32% of the studies evaluated
extra-pulmonary samples.
•
48% of the studies used
Stonebrink as a culture
medium for the growth of
Mycobacterium tuberculosis
complex species.
•
8% evaluated the risk of
zoonotic TB specifically in
children specifically in
children.
•
11% evaluated the risk of
zoonotic TB among TB patients
from rural areas.
Distribution of key study
characteristics
72.58%
53.23%
48.39%
32.26%
11.30%
8.06%
Preliminary Field Data - Zambia
• Recent retrospective study analyzed sputum samples from 917 patients
assumed to be infected with M. tb
• 8 patients with M. bovis, all of whom were cattle farmers.
• Currently have ongoing study looking at the rural Namwala district of
Zambia
• Sample includes 45 human patients diagnosed with TB
• 15 (33%) have been initially classified as infected with M. bovis based
on culture morphology (cultured on Stonebrink medium)
• 13 of these patients indicated that they consume raw milk
• Currently, strain typing is pending to confirm M. bovis
One Health Collaboration - Kenya
• Collaborating with physicians in Kenya that noticed monoresistance to pyrazinamide
(PZA) among TB patients in rural areas.
• 2012: 6% of M. tb complex isolates were monoresistant to PZA
• Role of socio-cultural practices & the true risk of M. bovis infection in these rural
communities of Kenya.
Dr. Meghan McInerney
(M.D. DTM&H)
Fellow, Pulmonary and
Critical Care Medicine
Indiana University
Dr. Jane Carter (MD)
Associate Professor of Medicine
The Union President
MD, Division Global Public
Health, University of California,
San Diego
Conclusions
• There is considerable variation in the risk
estimates reported for M. bovis infection
among human TB patients (range 0-45%).
• Key study characteristics differ
considerably, which can have an effect on
the risk estimates reported by different
studies.
• Rural communities are
underrepresented in the current
literature.
• A considerable amount (>50%) of
studies did not use the recommended
culture medium to grow M. bovis, nor
were extra-pulmonary samples
evaluated.
Implications
• Epidemiology, pathology, and
treatment challenges associated with
M. bovis infection among humans are
significant.
Studies are needed to assess the risk of
zoonotic TB among populations in
regions where socio-cultural and
economic factors increase the risk
posed by this zoonosis.
•

Patient enrollment, sampling
procedures, and laboratory
protocols need to be carefully
considered.
Acknowledgements
• Dr. Francisco Olea-Popelka
Questions?
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References
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