Zoonotic Tuberculosis at the

Human-Livestock-Wildlife

Interface

Meghan Gibas

Colorado State UniversityCollege 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. bovisis 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.

11.30% 8.06%

48.39%

72.58%

32.26%

53.23%

Distribution of key study characteristics

• 32% of the studies evaluated extra-pulmonary samples.

• 48% of the studies used Stonebrink as a culture medium for the growth ofMycobacterium 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.

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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