Bovine tuberculosis

Mycobacterium bovis as the Agent of Human Tuberculosis: Public Health Implications 23

2.3.7 HIV/AIDS

Human-to-human transmission of M. bovis has
been shown to occur among HIV-positive
patients (Bouvet et al., 1993). Of particular con-
cern is the transmission of M. bovis strains resis-
tant to not only pyrazinamide, but other first-line
anti-TB drugs such as isoniazid in HIV-positive
persons (Dupon and Ragnaud, 1992; Bouvet
et al., 1993; Blázquez et al., 1997; Samper et al.,
1997; Cosivi et al., 1998; Fortún et al., 2005)
rendering the standard four-drug regimen of iso-
niazid, rifampicin, ethambutol and pyrazinamide
much less effective. A study in the US identified
that TB caused by M. bovis was common among
persons living with HIV and was strongly associ-
ated with both Hispanic ethnicity and dissemi-
nated disease with abdominal involvement (Park
et al., 2010). In this study, as in others conducted
previously in the US (Hlavsa et al., 2008; Rodwell
et al., 2008), the authors concluded that unpas-
teurized dairy products were a likely source of
acquisition and that HIV care providers should
be aware of this risk and counsel patients appro-
priately. Again, while the resistance pattern is
not unique to HIV-positive persons, their com-
promised immune systems increase the likeli-
hood of recent infection progressing rapidly to
severe clinical M. bovis disease and transmission
to others. With 74% of HIV-related TB cases
being in sub-Saharan Africa (WHO, 2016) as
well as 70% of zoonotic TB cases caused by
M. bovis estimated to occur in Africa (Müller
et al., 2013; WHO, 2015b), the potential overlap
of HIV and M. bovis is concerning.

2.4 Clinical challenges posed

by M. bovis as a causal

agent of human TB

Data on the clinical impact of M. bovis as a cause
of human TB are predominantly available from
high-income countries where access to labora-
tory diagnostic tools allows speciation of the
M. tuberculosis complex. It is important that cli-
nicians, health workers and public health offi-
cials recognize the unique epidemiologic and
clinical features of zoonotic TB.

2.4.1 Antimicrobial resistance

Inherent pyrazinamide (PZA) resistance

An additional complication that zoonotic TB

patients face is that M. bovis is inherently resis-

tant to pyrazinamide (O’Donohue et al., 1985;

Niemann et al., 2000), a key medication in the

standard first-line TB treatment regimen, thus

presenting a special challenge for patient treat-

ment and recovery. Unfortunately, most TB

patients in the world begin TB treatment based

on either clinical symptoms or sputum smear

microscopy, without knowledge of drug

susceptibility or identification of the causative

Mycobacterium species, increasing the risk of

inadequate treatment of patients with undiag-

nosed M. bovis. As a result, patients with TB due

to M. bovis may receive sub-optimal treatment,

which could select for further resistance and

explain higher mortality rates in M. bovis-

infected patients (de la Rua-Domenech, 2006;

Rodwell et al., 2008). Globally in 2014, only

12% of the 2.7 million new bacteriologically-

confirmed TB cases were tested for drug resis-

tance (WHO, 2015a).

In Belgium, Allix-Beguec et al. (2010) con-

cluded that the absence of prompt identification

of M. bovis in an adult case had adverse conse-

quences for clinical management. Specifically,

the authors indicated that due to the lack of

speciation of the Mycobacterium, ‘pyrazinamide

was inadequately administered in the 2 months

of induction chemotherapy and, worst, was

inappropriately used to replace isoniazid in

the follow-up treatment because of toxic

hepatitis’. In addition, this case constitutes an

additional example of the persistent signifi-

cance of M. bovis as a zoonotic pathogen, even

in countries such as Belgium which has

been declared officially free of cattle TB since

2003. In the US, the recommendation for 9
      months of antimicrobial therapy utilizing
      isoniazid and rifampicin for TB patients infected
      with M. bovis instead of the standard four-drug
      6-month regimen for M. tuberculosis (CDC,
      2003; LoBue and Moser, 2005) presents addi-
      tional challenges due to decreased patient
      adherence and increased costs associated with
      prolonged treatment.