REVIEW ARTICLE

The Risk of Tuberculosis Transmission to Free‐Ranging Great ApesTIFFANY M. WOLF1,2*, SRINAND SREEVATSAN3, DOMINIC TRAVIS3, LAWRENCE MUGISHA4,5,AND RANDALL S. SINGER1

1Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul,Minnesota2Minnesota Zoological Gardens, Apple Valley, Minnesota3Department of Veterinary Population Medicine, College of Veterinary Medicine, University of Minnesota, St. Paul,Minnesota4College of Veterinary Medicine, Animal Resources and Biosecurity, Makerere University, Kampala, Uganda5Conservation and Ecosystem Health Alliance (CEHA), Kampala, Uganda

Pathogen exchange between humans and primates has been facilitated by anthropogenic disturbances,such as changing land use patterns, habitat destruction, and poaching, which decrease population sizesand increase levels of primate–human interaction. As a result, human and domestic animal diseaseshave become a recognized threat to endangered primate populations. Tuberculosis is a major globalhuman and animal health concern, especially in equatorial Africa where many of the remaining free‐living great ape populations exist in proximity with exposed and/or infected human populations andtheir domestic animals. Increased anthropogenic pressure creates an opportunity for the anthro-pozoonotic spread of this disease. This review examines current evidence of the risk of tuberculosistransmission to great apes, the benefits and limitations of current detection methods, the impact ofcurrent great ape conservation and management strategies on this risk, and the need for an ecosystemhealth‐based approach to mitigating the risks of tuberculosis transmission to great apes. Am. J.Primatol. 76:2–13, 2014. © 2013 Wiley Periodicals, Inc.

Key words: great apes; tuberculosis; anthropozoonotic disease transmission

INTRODUCTION

In 2011, there were an estimated 8.7 million newcases of tuberculosis among humans worldwide, witha global prevalence of approximately 170 cases per100,000 people [WHO, 2012]. This global pandemic isprimarily caused by Mycobacterium tuberculosis, ofwhich humans are the natural host, although otherpathogenic mycobacteria of the M. tuberculosisComplex (MTC), such as Mycobacterium africanumand Mycobacterium bovis, also play a role in humaninfection [Cosivi et al., 1999; Gagneux, 2012; Kazwalaet al., 2001]. Tuberculosis is predominantly a pulmo-nary disease, spread when bacteria are expelled fromthe lungs with the onset of active disease, but it mayalso present as extra‐pulmonary disease involvingother organs of the body [WHO, 2012]. Amonghumans infected with M. tuberculosis, only about5–10% develop active disease and become infectious,while the remainder either eliminate infection orremain latently infected and do not transmit infec-tion [Gagneux, 2012; Palomino et al., 2007;WHO, 2012]. However, those co‐infected with humanimmunodeficiency virus (HIV) are much more likelyto develop active disease [Cosma et al., 2003;Gagneux, 2012; Palomino et al., 2007; WHO, 2012].Advances in molecular research are revealing much

more genomic heterogeneity of M. tuberculosisstrains than previously recognized [Cosma et al.,2003; Gagneux, 2012; Hershberg et al., 2008;Sreevatsan et al., 1997]. This genomic diversity hasbeen linked to function and may explain some of theobserved differences in infection outcome, diseaseprogression, and transmission among infected hu-mans [De Jong et al., 2008; Gagneux, 2012; Hersh-berg et al., 2008; Portevin et al., 2011].

Contract grant sponsor: Zoetis/Morris Animal FoundationVeterinary Research Fellowship; contract grant sponsor: Con-sortium on Law and Values in Health, Environment & the LifeSciences of the University of Minnesota; contract grant sponsor:Minnesota Zoo; contract grant sponsor: USDA‐NIFA SpecialsGrant on Bovine Tuberculosis; contract grant sponsor: Veter-inary Population Medicine Department of the University ofMinnesota’s College of Veterinary Medicine

Conflicts of interest: None

�Correspondence to: Tiffany M. Wolf, 205 Veterinary SciencesBuilding, University of Minnesota, 1971 Commonwealth Ave-nue, St. Paul, MN 55108. E‐mail: wolfx305@umn.edu

Received 8 December 2012; revised 25 July 2013; revisionaccepted 29 July 2013

DOI: 10.1002/ajp.22197Published online 5 September 2013 in Wiley Online Library(wileyonlinelibrary.com).

American Journal of Primatology 76:2–13 (2014)

© 2013 Wiley Periodicals, Inc.

Until recently, infection withM. tuberculosis orany other MTC member has never been detected infree‐ranging great ape populations, and manyargue that contact between great apes and M.tuberculosis infected humans is insufficient fortransmission to susceptible free‐ranging greatapes. However, as tuberculosis remains a majorglobal human health threat and contact ratesbetween humans and great apes increase withhabitat encroachment, forest fragmentation, andconservation‐driven research and ecotourism, therisk of tuberculosis transmission from humans togreat apes must be continuously assessed. More-over, transmission pathways from humans throughother animal hosts whose contact with humans andgreat apes are high must be closely evaluated.Spillover of MTC infection from domestic animalsand possibly humans into free‐living monkeypopulations is well documented and may be animportant source of transmission of human ordomestic animal tuberculosis infection to greatapes [Keet et al., 2000; Sapolsky & Else, 1987;Tarara et al., 1985; Wilbur et al., 2012]. A recentdiagnosis of tuberculosis infection in a wildchimpanzee by a novel MTC strain underscoresthe knowledge gaps on the epidemiology andimpact of tuberculosis to primate conservation[Coscolla et al., 2013]. The existence of great apespecies in small, isolated populations requires thatthe long‐term impact of tuberculosis transmissionon population persistence be considered whencharacterizing this risk of disease caused bymembers of the MTC. Here we review reports ondisease transmission, great ape conservation strat-egies, tuberculosis infection in non‐human pri-mates, and current methods of detection todemonstrate that tuberculosis transmission is arealistic threat for great ape conservation. Further,we identify specific areas where more research isneeded to fully characterize this disease threat forgreat ape populations and demonstrate the need foran ecosystem health‐based approach to mitigatethis transmission risk. This review focuses onAfrican populations of great apes, although manyof the arguments presented here have applicationin Asian populations as well.

DISCUSSIONDisease Transmission Between Humans andGreat Apes

Most extant great ape populations exist infragmented populations distributed across equatori-al Africa. These populations include Eastern (Gorillaberingei) and Lowland (Gorilla gorilla) gorillas,bonobos or pygmy chimpanzees (Pan paniscus), andcommon chimpanzees (Pan troglodytes) [Fruth et al.,2008; Oates et al., 2008; Robbins &Williamson, 2008;Walsh et al., 2008]. Eastern gorillas, of which there

are two subspecies, mountain gorillas (G. b. beringei)and Eastern lowland gorillas (G. b. graueri) can befound in Uganda, Rwanda, and the DemocraticRepublic of Congo (DRC) [Robbins & Williamson,2008]. Lowland gorilla (G. gorilla) populations, alsoconsisting of two subspecies (G. g. gorilla and G. g.diehli), exist in forest fragments of several westernAfrican countries, such as Angola, Nigeria, Came-roon, Congo, and Gabon [Walsh et al., 2008]. Whilebonobo populations are limited to DRC, commonchimpanzee populations, consisting of four subspe-cies (Pan troglodytes verus, P. t. ellioti, P. t. troglo-dytes, and P. t. schweinfurthii), are the most widelydistributed of the great apes, stretching discontinu-ously across equatorial Africa from southern Senegalto western Tanzania and Uganda [Fruth et al., 2008;Oates et al., 2008]. All of these great ape populationsare declining and are currently listed by theInternational Union for Conservation of Nature asendangered or critically endangered [Fruth et al.,2008; Oates et al., 2008; Robbins &Williamson, 2008;Walsh et al., 2008]. Each of these species arethreatened by infectious diseases such as Ebola anda range of human pathogens, although differences inspecies behavior and social organization may beinfluencing exposure to and population impactsassociated with certain pathogens [Nunn et al.,2003, 2007].

There is accumulating evidence indicating thatgreat apes are exposed to and, in some cases, sufferdisease from human and domestic animal pathogens[Kaur et al., 2008; Köndgen et al., 2008; Palacioset al., 2011; Rwego et al., 2008; Whittier, 2009;Williams et al., 2008]. There have been numerousindependent reports of disease outbreaks amonggreat ape populations across Africa in which patho-gens have been linked to transmission from humans(Table I). In many of these epidemics, a definitivediagnosis of the etiological agent was not conclusivelydetermined. In these cases, transmission fromhumans is speculative, based on circumstantialevidence associating animal behavior, clinical dis-ease signs, and contact with local infected humans.However, in recent years molecular epidemiologicalmethods have significantly improved our abilities tomore definitively determine the role of humanpathogen transmission in the occurrence of infectiousdisease outbreaks among great apes. For example,several outbreaks of respiratory disease in chimpan-zees of Taï National Forest, Côte d’Ivoire weredetermined by molecular techniques to be causedby human metapneumovirus (HMPV) and respirato-ry syncytial virus (HRSV) [Köndgen et al., 2008,2010]. Gene sequencing and phylogenetic analyses ofHMPV and HRSV PCR products revealed virusstrains to be closely related to those circulating inthe human population, providing the first evidencefor human disease transmission into a great apepopulation. Subsequently, HMPV infection has also

Am. J. Primatol.

Risk of Tuberculosis for Wild Great Apes / 3

TABLE

I.In

fectiousDisea

seEpid

emicsof

Fre

e‐Ran

gingGre

atApePop

ulation

sLin

ked

toHuman

s

Outbrea

kDate

Spe

cies

Location

Morbidity

(%)/m

ortality

aEtiolog

yRefs.

Paralytic

diseas

e19

66Chim

panz

ees

Gom

beNational

Park,

Tan

zania

20/6

Susp

ectedpo

lio

William

set

al.[20

08],Gooda

ll[198

6]Respiratory

diseas

e19

68Chim

panz

ees

Gom

beNational

Park,

Tan

zania

63/4

Und

iagn

osed

,Steptococcu

spn

eumon

iaean

dS.p

yogenes

(200

0ou

tbreak

)

William

set

al.[20

08],Mleng

eya

[200

1]

1987

40/9

2000

75/2

Respiratory

diseas

e19

88Mou

ntain

gorillas

Virun

gaVolcano

es,

Rwan

da81

/3Susp

ectedmea

sles

andMycop

lasm

apn

eumon

iae

Sho

lley

[198

9],H

asting

set

al.

[199

1],H

omsy

[199

9]Respiratory

diseas

e19

90Mou

ntain

gorillas

Virun

gaVolcano

es,

Rwan

da61

/1Susp

ectedpa

ramyx

ovirus

Hom

sy[199

9]

Dermatitis

1996

Mou

ntain

gorillas

Bwindi

Impe

netrab

leNational

Park,

Uga

nda

100/1

Scabies

Kalem

a‐Ziku

soka

etal.[20

02]

Respiratory

diseas

e19

99b

Chim

panzees

Taï

Nationa

lForest,

Coted’Ivoire

100/6

Hum

anresp

iratorysync

ytialviru

san

dmetap

neu

mov

irus

Kön

dgen

etal.[20

08]

2004

b10

0/8

2006

b92

/1Respiratory

diseas

e20

03Chimpa

nzees

Mah

aleMou

ntains

National

Park,

Tan

zania

98/4

Hum

anmetap

neum

ovirus

Kau

ret

al.[200

8]

2005

52/2

2006

b48

/12

Respiratory

diseas

e20

09b

Mou

ntain

gorillas

Virun

gaVolcano

es,

Rwan

da92

/2Hum

anmetap

neum

ovirus

Palacioset

al.[201

1]

aMorbidity

isrepr

esen

tedas

thepe

rcen

tage

ofthetotalpo

pulation

that

demon

stratedclinical

sign

sof

diseas

e,wherea

smortality

isthetotalnumbe

rof

deathsas

sociated

withtheep

idem

ic.

bThe

reis

strong

molecular

eviden

cethat

theetiologicalag

ents

associated

withtheseou

tbreak

soriginated

from

hum

ans.

Am. J. Primatol.

4 / Wolf et al.

been associated with separate respiratory outbreaksamong chimpanzees of Mahale Mountains NationalPark, Tanzania and mountain gorillas of VirungaMassif, Rwanda using PCR and phylogenetic analy-ses [Kaur et al., 2008; Palacios et al., 2011]. Thesefindings demonstrate that sufficient contact betweenhumans and great apes exists which enables thetransmission of certain human pathogens, but muchremains to be learned about such contact, thedynamics of these transmission events, and if thesecoupling points between humans and great apeswould facilitate the transmission of other humanpathogens.

Microbial transmission from humans to free‐living great apes and other primates has also beendocumented beyond the scope of outbreak investiga-tion. Several studies of antimicrobial resistance andgenetic relatedness of enteric bacteria have shownthat bacterial isolates from primates living in closeproximity to humans share similar antimicrobialresistance patterns and are more genetically relatedto isolates from humans, as opposed to isolates fromprimates not living in close proximity to humans[Goldberg et al., 2008; Rwego et al., 2008]. Thesestudies highlight the significance of environmentaltransmission of microorganisms and potential patho-gens between humans and great apes.

Besides patterns of contact arising from anthro-pogenic impacts on the natural environment (e.g.,habitat fragmentation and increased human densi-ties surrounding great ape habitat), pathogentransmission has been associated with humanhabituation of great apes for research and ecotour-ism [Homsy, 1999; Köndgen et al., 2008]. Humanhabituation, a tool utilized in the conservation ofendangered great apes, entails the conditioning ofthese animals to close encounters with humanobservers. The benefits of human habituation togreat ape survival have been realized through thereduction of poaching and habitat loss in areaswhereresearch and ecotourism exist [Campbell et al., 2011;Köndgen et al., 2008; Pusey et al., 2007]. Thus, tomaintain the benefits of habituation and mitigatethe disease risks, managersmust consider the healthof the humans in contact with these animals:tourists, researchers, park workers, and local hu-mans living in proximity or within the parks.

Tourists have been a primary focus in assessingdisease risks to great apes given their potential forintroducing new pathogens into an ecosystem[Homsy, 1999; Sandbrook & Semple, 2007; Woodfordet al., 2002]. However, it is important to note thatseveral disease outbreaks in great ape populations(Table I) have been attributed to transmission fromresearchers (e.g., HRSV and HMPV outbreaks in TaïNational Forest) or the local human population,including park workers (e.g., scabies, measles, polio)[Kalema‐Zikusoka et al., 2002; Köndgen et al., 2008;Sholley, 1989; Williams et al., 2008; Woodford et al.,

2002]. It has been shown that human behaviors, suchas defecating, urinating, poor waste disposal, andaerosol contamination through sneezing and cough-ing, within and in proximity to mountain gorillahabitat are a health risk to mountain gorillapopulations, with local communities posing thegreatest risk [Nizeyi et al., 2012]. Thus, as weconsider endemic disease risks to habituated greatapes, it becomes clear that contact between greatapes and local humans may pose a risk for thetransmission ofM. tuberculosis and other pathogenicmembers of the MTC, pathogens which may have ahigh prevalence in local African human and domesticanimal populations and which may have potentiallydevastating effects on great ape populations.

The Risk of Tuberculosis Transmission toGreat Apes

With an initial assessment of the risk oftuberculosis transmission from humans to greatapes, it may be hypothesized that the risk isfundamentally related to the incidence of activeinfection in the local human or animal populationswith which great apes have contact. In themost basicSusceptible‐Infectious‐Recovered (SIR) transmissionmodels, contact rate and increasing incidence ofinfectiousness drive transmission. Thus, in areaswhere human or domestic animal tuberculosis ishigher and there is contact with great apes or otherprimates, higher transmission risk would be ex-pected. Conversely, in areas where human/domesticanimal tuberculosis and/or great ape contact is lower,the risk would inherently be lower. According to the2012 WHO Global Tuberculosis Control report,among the 8.7 million global incident cases of humantuberculosis, 24% of these occurred in Africa[WHO, 2012]. Furthermore, the geographical distri-bution of African great ape habitat falls withincountries that have some of the world’s highest ratesof human tuberculosis, ranging from 50 to over 300incident cases per 100,000 people (Fig. 1)[WHO, 2012]. These statistics as well as the highprevalence of HIV co‐infection among humans in thisregion raises additional concern for transmissionrisk, as co‐infection with HIV generally results in ahigher likelihood of active tuberculosis. Furthermore,recent evidence of MTC DNA among populations offree‐ranging synanthropic macaques demonstratesthat frequent human contact and high tuberculosisprevalence within the human population increasesthe risk of tuberculosis for non‐human primatepopulations [Wilbur et al., 2012]. Unfortunately,the epidemiology of tuberculosis is not so simple as tobe explained by basic SIR models. For instance, mosthuman infections are latent and therefore notinfectious, which complicates assessments of risk.Additionally, the contact needed for tuberculosis

Am. J. Primatol.

Risk of Tuberculosis for Wild Great Apes / 5

transmission among humans is typically close andsustained, which is generally not characteristic of thecontact between humans and free‐living great apes.Thus, increases in human tuberculosis incidence willnot necessarily be linearly related to the tuberculosisrisk for great apes, particularly if other hosts areinvolved in transmission of infection. Moreover,much remains to be understood about the observedvariation in susceptibility and transmission ofdifferent M. tuberculosis strains among humansand the genetic drivers of these events beforereasonable predictions can be made about risk toprimates [Gagneux, 2012]. However, as basic scienceand epidemiological research enhances our under-

standing of this variability among humans, ourability to predict this risk for primate populationswill also advance.

A survey conducted in 2000 of local inhabitants ofBwindi Impenetrable Forest National Park, Ugandafound that despite a high level of respiratorysymptoms in the region, many people were not testedfor tuberculosis and infection status was largelyunknown [Guerrera et al., 2003]. These data suggestthat many cases of tuberculosis may go undetectedand untreated. This situation is slowly changing asglobal efforts and funding for tuberculosis control areincreasing, especially in areas of Africawith highHIVprevalence [WHO, 2012]. Since park workers

Fig. 1. Geographic distribution of great ape home range countries compared to the incidence of human tuberculosis in Africa. Datacontained in this map originated from Robbins &Williamson [2008], Oates et al. [2008], Walsh et al. [2008], and Fruth et al. [2008], andWHO [2012].

Am. J. Primatol.

6 / Wolf et al.

employed to protect great apes originate from theselocal communities, updated information on thetuberculosis status and awareness among thesecommunities would be valuable to both public healthand great ape conservation. While population man-agers generally recognize concern for tuberculosisintroduction and guidelines for tuberculosis testingamong park employees have been developed, employ-ee health and disease screening programs have notyet been widely adopted for park workers [Aliet al., 2004; WCS, 2005].

Many parks have established rules to reducepathogen transmission from humans to great apes,such as restricting great ape visitation by people whoare ill and coughing, or through vaccination[Homsy, 1999; Williamson & Macfie, 2010]. As M.tuberculosis is generally transmitted by the aerosoli-zation of infectious particles (through coughing,talking, or sneezing) that can be suspended in theair for hours before being inhaled, such park rulesshould prevent the transmission of this pathogen togreat apes from infectious people with pulmonarytuberculosis simply by eliminating contact[Baker, 1995]. Although this rule may not capturepeople infected with gastrointestinal tuberculosis,who may be shedding high numbers of organism intheir stool, other rules restricting defecation withingreat ape habitat should reduce such a risk [Rasheedet al., 2007; Sharma & Bhatia, 2004]. However, ashabitat use by non‐research and non‐tourist humansincreases, the risks of disease transmission that aremitigated by these rules might be expected toincrease. Additionally, in situations where parkworkers, researchers, or other local humans residewithin the park and great apes enter areas of humanhabitation, restricting visitation by ill humans maynot be enough to completely eliminate contact andtransmission that may occur within these areas ofhuman habitation. Furthermore, the use of vaccina-tion in humans as a preventative measure mayprovide a false sense of security, as bacille Calmette‐Guérin (BCG), the only vaccine available againsttuberculosis, does not reliably protect against pulmo-nary tuberculosis [Russell et al., 2010].

Indirect routes of transmission such as contami-nation and pathogen persistence in the environmentshould also be considered as possible pathways fortuberculosis transmission. Great apes that frequentareas of human habitation, either within or outside ofparks, may be at greatest risk for both direct andindirect transmission. For example, M. tuberculosis(as well as other respiratory pathogens) may betransmitted via interaction with contaminated ob-jects (i.e., fomites)—such as tissues or handkerchiefs—that capture the attention of curious great apes,which often touch, smell, and potentially consumesuch novel objects [Wallis & Lee, 1999; Woodfordet al., 2002]. In general, Mycobacterium species arewell adapted to survival in harsh environments, with

the lipid‐rich, protective cell wall, slow growth rate,and long dormancy [Baker, 1995; Chadwick, 1981;Palomino et al., 2007]. Environmental contaminationand fomites have been implicated in the transmissionof MTC organisms (e.g.,M. bovis,M. mungi) betweenwildlife, humans, and domestic animals [Alexanderet al., 2010; Courtenay et al., 2006; Tararaet al., 1985]. Further, other primate or wildlifespecies may serve as a vector for transmission oftuberculosis (human, bovine or other) into great apepopulations. The role of environmental, fomite, orvector species transmission in other human respira-tory pathogen outbreaks among great apes has notyet been assessed, but should be explored whenweighing the risks of tuberculosis transmission intogreat ape and other primate populations.

Another potential source of human tuberculosisfor free‐living great ape populations is the reintro-duction of rehabilitated great apes by primatesanctuaries. Great apes at these facilities originatefrom diverse locations throughout Africa in variousstates of health and have assorted histories ofhuman contact [Mugisha et al., 2011; Schoene &Brend, 2002]. These sanctuaries are challenged withmanaging injuries and illnesses in the face of limitedresources. Crowded conditions and animal stresscontribute to efficient disease transmission, andcross‐species transmission between animals andhuman caretakers is a significant concern. Thisconcern was exemplified in a recent study ofStaphylococcus aureus epidemiology in African sanc-tuaries where chimpanzees were found infected witha variety of human‐associated, multi‐drug resistantstrains of S. aureus, indicating transmission fromtheir human caretakers [Schaumburg et al., 2012b].Tuberculosis outbreaks have also been diagnosedwithin primate sanctuaries and are particularlyconcerning given the challenges of early detection,diagnosis, and management of infected individualswith limited resources [Unwin et al., 2012]. Thenumber of great apes turned over to sanctuaries formedical care and rehabilitation is increasing, as isinterest in reintroduction of these animals into theirnatural habitat. Given the current challenges ofdisease screening in these settings, rehabilitatedanimals would pose a significant risk for theintroduction of tuberculosis and other human patho-gens into presumably naïve free‐living populations.

Understanding pathogen transmission acrosshost species within an ecosystem is a complex task,particularly when several closely related pathogensare circulating and causing disease. This is certainlyan issue in human medicine, where closely relatedmembers of the Mycobacterium genus have beenresponsible for disease in humans. For example, M.bovis, the etiologic agent of bovine tuberculosis andclose relative ofM. tuberculosis in the MTC, has beendocumented in cases of extrapulmonary tuberculosisin rural Tanzania [Kazwala et al., 2001, 2006].

Am. J. Primatol.

Risk of Tuberculosis for Wild Great Apes / 7

Unfortunately, it is not easily distinguished from M.tuberculosis when culture is unavailable, thus itscontribution to the tuberculosis epidemic in humansis not fully understood [Cleaveland et al., 2007;Kazwala et al., 2001]. Moreover, despite a growingbody of evidence for the zoonotic potential ofM. bovis,developing countries often lack regulations forcontrol and prevention of infection in livestock, andgeneral knowledge regarding risks of infection arelacking [Cosivi et al., 1999; Michel et al., 2010].

The distinction betweenMycobacterium species isrelevant with regard to the source of transmission andhow these pathogens are transmitted between species.Although humans may be infected with and sufferdisease from eitherM. tuberculosis orM. bovis, amuchhigher prevalence of M. tuberculosis has been docu-mented in humans with tuberculosis [Kazwalaet al., 2001, 2006]. Additionally, the transmission ofM. tuberculosis among humans (e.g., via aerosolizedinfectious organisms) is generally different than thetransmission of M. bovis to humans (e.g., via unpas-teurizedmilk and exposure to infected animal tissues)[Baker, 1995; Cosivi et al., 1999]. On the contrary,livestock with tuberculosis are typically infected withM. bovis and not M. tuberculosis, and are generallyinfected by M. bovis through aerosolized infectiousorganisms from conspecifics or through exposure toinfectious materials such as feces and urine fromalternative hosts sharing their environment (asobserved with wildlife hosts such as badgers inBritain) [Courtenay et al., 2006; Morris et al., 1994].This distinction between Mycobacterium species be-comes importantwhendiscussing transmission risk asthese organisms are transmitted between species andthrough the environment by different mechanismsand pathways, which in turn impacts the risk ofexposure to these pathogens for primates within theirown environment. Therefore, to further considerstrategies that might reduce the risk of disease inprimate populations, it is important to evaluateMycobacterium species‐specific differences (includinginfected source populations) in transmission thatmight impact primate exposure.

Given the phylogenetic similarity of humans andgreat apes, as well as evidence ofM. bovis infection infree‐living baboon populations, it may be presumedthat great apes share a similar risk of infection byM.bovis [Keet et al., 2000; Sapolsky&Else, 1987; Tararaet al., 1985]. Species such as baboons, whose behaviorbrings them in frequent contact with humans,livestock, and great apes, might be potential couplingpoints for disease transmission across some of thesepopulations that might not otherwise come into directcontact [Keet et al., 2000; Müller‐Graf et al., 1997;Murray et al., 2000]. Thus, to fully understand therisk of tuberculosis transmission to great apes, theprevalence of M. bovis in local livestock as well otherwildlife species (e.g., baboons or other monkeys) mustalso be considered.

Tuberculosis Infection in Primates

Much of our understanding of naturally acquiredtuberculosis infection in great apes and monkeysoriginates from observations of captive animals[Diniz et al., 1983; Loomis, 2003; Michel et al.,2003; Michel & Huchzermeyer, 1998]. Clinical signsare absent in latent infection, but quite varied withactive disease, ranging from nonspecific abnormali-ties, such as anorexia, lethargy, or weight loss torespiratory signs such as tachypnea or coughing[Diniz et al., 1983; Michel et al., 2003]. Extra‐pulmonary infection results in changes in healthassociated with the tissue of infection (e.g., drainingabscessation, hemorrhagic diarrhea) [Michel et al.,2003]. Pathologic lesions may be characterized byinfiltrates or cavitations of the lungs or other infectedtissues, including lymph nodes, bone, kidney, centralnervous system, and others. Within the realm ofcaptive management, there is much concern for thetransmission of tuberculosis from humans to greatapes, due to the recognized susceptibility of greatapes to tuberculosis [Loomis, 2003; Michel &Huchzermeyer, 1998]. It is difficult, however, topredict how susceptibility, disease, and transmissionof tuberculosis as observed among captive great apesmight translate to free‐ranging populations. Certain-ly stress, social interactions, human contact, andactivity patterns can strongly influence susceptibilityand disease; however, the difficulties in measuringthese factors for direct comparison of captive andfree‐ranging populations challenges our ability toextrapolate from our knowledge of this disease incaptivity to estimate the risk of infection andpotential impacts on free‐ranging populations.

A recent diagnosis of MTC infection in a wildchimpanzee is our first glimpse of tuberculosisinfection in free‐ranging great apes [Coscolla et al.,2013]. In this report, researchers describe theidentification of a genetically distinct MTC strain oftuberculosis, most closely related to Lineage 6 (i.e.,M. africanum West‐Africa type‐2), on a routinenecropsy of an aged female chimpanzee killed by aleopard in Taï National Forest. Aside from deterio-rating body condition over a period of years, thereport indicated no other clinical signs associatedwith the extra‐pulmonary tuberculosis infection. Theinvestigators further report that despite extensivenecropsies and molecular screens of other chimpan-zees in the region, this appears to be a unique finding,and it is yet unknown as to whether this novel strainis a chimpanzee‐specific pathogen or one transmittedfrom another primate or animal host. Although mostclosely related to human‐associated strains of tuber-culosis, the results of this investigation do not suggestthat infection originated from humans. Undoubtedly,this finding warrants more active investigations intothe prevalence of this pathogen and the geneticdiversity of tuberculosis infection among free‐living

Am. J. Primatol.

8 / Wolf et al.

primates to better understand the epidemiology andimpact of tuberculosis infection to the conservation ofthese populations.

There are inherent challenges in positivelyidentifying tuberculosis in great apes. Multiplediagnostic modalities, typically relying on the dem-onstration of tissue lesions, host immune responses,or culture of the organism, are required for thediagnosis in great apes by standard methods [Linet al., 2008; Miller, 2008]. Reliance on thesetraditional tuberculosis test methods makes tuber-culosis surveillance impractical given the need foranimal handling and anesthesia for collection of thenecessary diagnostic specimens. Thus, the detectionof tuberculosis in free‐ranging species has beenmostly limited to post‐mortem diagnosis, at whichtime transmission of tuberculosis may be welladvanced through a social primate group. Giventhese limitations, without systematic monitoring ofpopulation health accompanied by recovery and post‐mortem examination of all carcasses, a low level oftuberculosis infection among a great ape populationmight go undetected. To overcome this potentialproblem, consideration must be given to the applica-tion of molecular methods of pathogenic organismdetection in the development of non‐invasive meth-ods of tuberculosis diagnosis.

Non‐invasive sampling refers to the collection ofbiological samples without the need for animalhandling or anesthesia. Such methods have beenuseful in the screening of saliva, feces and urine forsystemic, gastrointestinal, and respiratory patho-gens of great ape populations [Gillespie et al., 2010;Kaur et al., 2008; Keele et al., 2009; Köndgenet al., 2010; Liu et al., 2008; Makuwa &Souquiere, 2003; Rudicell et al., 2010; Schaumburget al., 2012a]. Readers are referred to excellentreviews of infectious diseases of free‐living great apesand noninvasive sampling methods for the screeningof a variety of pathogens [Calvignac‐Spenceret al., 2012; Gillespie et al., 2008; Leendertzet al., 2006]. Accordingly, there are several molecularmethods that may be applied to such samples and beuseful in the detection of tuberculosis infection(Table II).

The collection of saliva samples of great apesfrom what is commonly referred to as “wadges,” ormasticated clumps of forest food, has found use ingenetic research of free‐living great apes and hasmore recently been employed in noninvasive diseasescreening [Inouse et al., 2007; Schaumburget al., 2012a; Shimada et al., 2004; Smileyet al., 2010]. Saliva samples from animals withclinical signs of disease could be utilized for thedetection and genotyping of M. tuberculosis throughculture and/or commonly employed techniques suchas IS6110 PCR‐RFLP, spoligotyping, or mycobacteri-al interspersed repetitive unit‐variable numbertandem repeat (MIRU‐VNTR) genotyping [Sankaret al., 2011;Wilbur et al., 2012]. These techniques areuseful in distinguishing M. tuberculosis from infec-tion with other MTC strains. In human medicine,mannose‐capped lipoarabinomannan (LAM), a cellwall component of pathogenicmycobacteria, has beenutilized as a urine biomarker of tuberculosis infection[Hamasur et al., 2001]. The utility of this biomarkerin the diagnosis of infection in humans has beenlimited by low sensitivity and specificity, although ithas shown greater accuracy in patients co‐infectedwith HIV [Peter et al., 2010]. The usefulness of LAMin the detection of tuberculosis in non‐humanprimates has yet to be determined. Urine collectionis a realistic option for non‐invasive sample collec-tion, having been used in other disease surveys; thus,it is reasonable to consider LAM as a possiblebiomarker for non‐invasive tuberculosis detectionin great apes [Leendertz et al., 2006]. Fecal samplesare the most readily available and easily attainablebiological samples of free‐ranging great apes. Thedetection of fecal antibodies against pathogenicorganisms has not been widely utilized for diseasescreening in primates; however, methods for fecalantibody detection have proven successful for thenon‐invasive detection of Simian Immunodeficiencyvirus and Simian Foamy virus in wild chimpanzees[Keele et al., 2009; Liu et al., 2008]. Given thedevelopment of a detectable humoral immune re-sponse to tuberculosis in primates, the detection ofanti‐tuberculosis antibodies in fecesmay be a feasibleoption for diagnosis [Lin et al., 2008; Lyashchenko

TABLE II. Non‐Invasive Sampling and Potential Methods for Tuberculosis Detection

SamplePotential target ordetection method Limitations

Saliva Culture and genotyping Infected individual must be infectious for the detection of organisms by culture orPCR, thus latent infection may go undetected. Possible low sensitivity associatedwith antibody detection

Mycobacterial PCRAntibodies

Urine LAM Low sensitivity and specificity in humansFeces Culture and genotyping Infected individual must be infectious for the detection of organisms by culture or

PCR, thus latent infection may go undetected. Possible low sensitivity associatedwith antibody detection; antibodies present in swallowed sputum may bedenatured in the stomach

Mycobacterial PCRAntibodies

LAM, lipoarabinomannan.

Am. J. Primatol.

Risk of Tuberculosis for Wild Great Apes / 9

et al., 2007]. Hence, exploration into fecal antibodydetection may be warranted as another option fornon‐invasive tuberculosis screening in great apes.Alternatively, fecal culture or molecular detection ofmycobacterial DNA in the feces of great apes offersanother opportunity for the diagnosis of disease.Recent studies among humans with active pulmo-nary tuberculosis reveal approximately 50% sensi-tivity and 100% specificity for the detection of M.tuberculosis by stool culture, and even highersensitivity using molecular detection (e.g., IS6110PCR‐RFLP) [Cordova et al., 2010; El Khéchineet al., 2009]. Therefore, culture and/or PCR may bea useful approach to pathogen detection in the feces ofgreat apes.

Amajor limitation to the detection of tuberculosisinfection by any of thesemethods is the latent stage ofdisease, in which case animals are not infectious anddetection of the organism and immune response isoften more challenging [Lin et al., 2008]. Alternative-ly, given the utility of these non‐invasively collectedspecimens for potential disease screening of otherpathogens, it is advantageous to move toward thedevelopment and validation of such methods. Cer-tainly, as these methods for non‐invasive tuberculo-sis detection improve and become more widelyavailable, a more comprehensive assessment oftuberculosis status among great ape populations(e.g., disease‐free or not) can be undertaken throughante‐mortem population surveillance or monitoring.

Directions for Future Research andMitigation of Tuberculosis Risk

Understanding and/or mitigating the risk oftuberculosis for the conservation of great apepopulations requires an ecosystem health approach.M. tuberculosis is a human pathogen, and there isevidence of high prevalence among humans residingin close proximity to great ape habitats across theirhome ranges. Better estimates and understanding ofcontrol measures for this disease in local humanpopulations are needed for accurate estimation ofrisk to great ape populations with which they havecontact. Thus, it is essential to develop partnershipsamong conservation managers and those involved inhuman health at local and non‐governmental levels.Given the evidence of human respiratory diseases ingreat ape populations, it can be concluded that thenecessary contacts already exist between humansand great apes for successful disease transmission.Whether these contacts are sufficient for tuberculosistransmission has yet to be determined. Furthermore,the role of the environment in the transmission ofsuch pathogens remains unknown. Accordingly,epidemiological research into routes of transmissionof known human pathogens affecting great apepopulations are needed not only for protectingagainst specific disease, but also in understanding

and potentially predicting opportunities for M.tuberculosis transmission within these ecosystems.Certainly, the most promising means of protectinggreat apes from M. tuberculosis is by improving thehealthcare infrastructure among local human com-munities, thereby reducing the burden of humantuberculosis in these regions.

M. tuberculosis is, unfortunately, not the onlymycobacterial pathogen for which great apes may beat risk of infection. M. bovis, a known pathogen ofdomestic livestock and wildlife, not only causesdisease in humans, but has also spilled over intofree‐ranging monkey populations. Thus, understand-ing of the risk and prevention of M. bovis infection ingreat apes also requires efforts in the area of bovinetuberculosis. There is a significant need for regula-tion, surveillance, and control of bovine tuberculosisin developing countries, as well as education on thezoonotic potential of this pathogen. Endeavors tomeet such objectives could significantly reduce theimpact of this disease for humans and their livestock,as has been observed in developed countries, as wellas eliminate a disease risk to great ape populations.Until these needs are met, however, estimates of M.bovis levels in local livestock populations andpotential routes of transmission are necessary tocharacterize this disease risk to great apepopulations.

M. tuberculosis is an old pathogen, originating inAfrica [Cosma et al., 2003; Gagneux, 2012]. Thispathogen’s co‐evolution with its human host iscomplex and there is much we are still learningabout variability of infection, host response, distribu-tion, and genetic and functional diversity [Cosmaet al., 2003; Gagneux, 2012]. Likewise, similarobservations of variations in infection and hostresponse among primates have yet to be fullyexplored. Combined with historical limitations ofdiagnosing tuberculosis infection in free‐rangingprimate specie, it cannot be known with certaintythat this pathogen is not already present in thesepopulations nor the full extent to which other MTCmembers (such as “Chimpanzee bacillus,” reported byCoscolla et al.) infect these populations [Coscollaet al., 2013]. The impact of tuberculosis and thedynamics of co‐infection with other diseases (e.g.,SIV) on the persistence of free‐ranging primatepopulations cannot be fully assessed without thedevelopment and employment of sensitive andreliable means for detecting infection and character-izing the pathogen.

As long as tuberculosis continues as a significanthuman and livestock disease, there is inherent risk oftransmission to remnant great ape populations withwhich there is human contact. Accordingly, just asprotection of these populations against threats offurther habitat loss and poaching is ensured throughconservation and research activities, we must en-deavor to enhance our understanding and mitigate

Am. J. Primatol.

10 / Wolf et al.

the risks of tuberculosis and other human anddomestic animal pathogens that equally threatenthe persistence of these populations.

ACKNOWLEDGMENTS

Exploration into the risk of tuberculosis forhabituated great apes is supported in part by theZoetis/Morris Animal Foundation Veterinary Re-search Fellowship, the Consortium on Law andValues in Health, Environment & the Life Sciencesof the University of Minnesota, the Ulysses S. SealConservation Fund of the Minnesota Zoo, the USDA‐NIFA Specials grant on bovine tuberculosis, and theVeterinary Population Medicine Department of theUniversity of Minnesota’s College of VeterinaryMedicine. The authors also thank the two AmericanJournal of Primatology reviewers who providedinsightful and thought‐provoking comments andrecommendations that contributed to the develop-ment of a more complete manuscript. This manu-script adhered to the American Society ofPrimatologists’ Principles for the Ethical Treatmentof Primates.

REFERENCESAlexander KA, Laver PN, Michel AL, et al. 2010. Novel

Mycobacterium tuberculosis complex pathogen, M. mungi.Emerg Infect Dis 16:1296–1299.

Ali R, Cranfield M, Gaffikin L, et al. 2004. Occupational healthand gorilla conservation in Rwanda. Int J Occup EnvironHealth 10:319–325.

Baker S. 1995. Airborne transmission of respiratory diseases. JClin Eng 20:401–406.

Calvignac‐Spencer S, Leendertz SAJ, Gillespie TR, LeendertzFH. 2012. Wild great apes as sentinels and sources ofinfectious disease. Clin Microbiol Infect 18:521–527.

Campbell G, Kuehl H, Diarrassouba A, N’Goran P, Boesch C.2011. Long‐term research sites as refugia for threatened andover‐harvested species. Biol Lett 7:723–726.

Chadwick M. 1981. Mycobacteria. Boston: Wright/PSG. 114 p.Cleaveland S, Shaw D, Mfinanga S, et al. 2007.Mycobacterium

bovis in rural Tanzania: risk factors for infection in humanand cattle populations. Tuberculosis 87:30–43.

Cordova J, Shiloh R, Gilman RH, et al. 2010. Evaluation ofmolecular tools for detection and drug susceptibility testingof Mycobacterium tuberculosis in stool specimens frompatients with pulmonary tuberculosis. J Clin Microbiol48:1820–1826.

Coscolla M, Lewin A, Metzger S, et al. 2013. Novel Mycobacte-rium tuberculosis complex isolate from a wild chimpanzee.Emerg Infect Dis. Available online ahead of print: http://dx.doi.org/10.3201/eid 1906.121012

Cosivi O, Grange J, Daborn C, et al. 1999. Zoonotic tuberculosisdue to Mycobacterium bovis in developing countries. EmergInfect Dis 4:59–70.

Cosma CL, Sherman DR, Ramakrishnan L. 2003. The secretlives of the pathogenic mycobacteria. Ann Rev Microbiol57:641–676.

Courtenay O, Reilly LA, Sweeney FP, et al. 2006. IsMycobacterium bovis in the environment important for thepersistence of bovine tuberculosis? Biol Lett 2:460–462.

De Jong BC, Hill PC, Aiken A, et al. 2008. Progression to activetuberculosis, but not transmission, varies byMycobacterium

tuberculosis lineage in The Gambia. J Infect Dis 198:1037–1043.

Diniz L, Iwasaki M, Demartin B. 1983. Clinical aspects oftuberculosis in a chimpanzee. Vet Med Small Anim Clin78:1289–1291.

El Khéchine A, Henry M, Raoult D, Drancourt M. 2009.Detection ofMycobacterium tuberculosis complex organismsin the stools of patients with pulmonary tuberculosis.Microbiology 155:2384–2389.

Fruth B, Benishay J, Bila‐Isia I, et al. 2008. Pan paniscus.IUCN red list of threatened species. Version 2012.2.

Gagneux S. 2012. Host‐pathogen coevolution in humantuberculosis. Philos Trans R Soc Lond B Biol Sci 367:850–859.

Gillespie TR, Nunn CL, Leendertz FH. 2008. Integrativeapproaches to the study of primate infectious disease:implications for biodiversity conservation and global health.Am J Phys Anthropol Suppl 47:53–69.

Gillespie TR, Lonsdorf EV, Canfield EP, et al. 2010. Demo-graphic and ecological effects on patterns of parasitism ineastern chimpanzees (Pan troglodytes schweinfurthii) inGombe National Park, Tanzania. Am J Phys Anthropol143:534–544.

Goldberg TL, Gillespie TR, Rwego IB, Estoff EL, Chapman CA.2008. Forest fragmentation as cause of bacterial transmis-sion among nonhuman primates, humans, and livestock,Uganda. Emerg Infect Dis 14:1375–1382.

Goodall J. 1986. The chimpanzees of Gombe: patterns ofbehavior. Cambridge, MA: Belknap Press of HarvardUniversity Press. 673 p.

Guerrera W, Sleeman J, Jasper S, et al. 2003. Medical surveyof the local human population to determine possiblehealth risks to themountain gorillas of Bwindi ImpenetrableForest National Park, Uganda. Int J Primatol 24:197–207.

Hamasur B, Bruchfeld J, Haile M, et al. 2001. Rapid diagnosisof tuberculosis by detection of mycobacterial lipoarabino-mannan in urine. J Microbiol Methods 45:41–52.

Hastings B, Kenny D, Lowenstine LJ, Foster JW. 1991.Mountain gorillas and measles: ontogeny of a wildlifevaccination program. In: Proceedings of the AmericanAssociation of ZooVeterinarians annualmeeting; September28–October 3. Calgary, Canada: American Association of ZooVeterinarians. p 198–205.

HershbergR, LipatovM, Small PM, et al. 2008. High functionaldiversity in Mycobacterium tuberculosis driven by geneticdrift and human demography. PLoS Biol 6:e311.

Homsy J. 1999. Ape tourism and human diseases: how closeshould we get? Report of the Consultancy for the Interna-tional Gorilla Conservation Programme. 86 p. Availableonline at: http://wildpro.twycrosszoo.org/000ADOBES/D133Homsy_rev.pdf [accessed May 8, 2012].

Inoue E, Inoue‐Murayama M, Takenaka O, Nishida T. 2007.Wild chimpanzee infant urine and saliva sampled noninva-sively usable for DNA analyses. J Primatol 48:156–159.

Kalema‐Zikusoka G, Kock R, Macfie E. 2002. Scabies in free‐ranging mountain gorillas (Gorilla beringei beringei) inBwindi Impenetrable National Park, Uganda. Vet Rec150:12–15.

Kaur T, Singh J, Tong S, et al. 2008. Descriptive epidemiologyof fatal respiratory outbreaks and detection of a human‐related metapneumovirus in wild chimpanzees (Pan troglo-dytes) at Mahale Mountains National Park, WesternTanzania. Am J Primatol 70:755–765.

Kazwala R, Daborn C, Sharp J, et al. 2001. Isolation ofMycobacterium bovis from human cases of cervical adenitisin Tanzania: a cause for concern? Int J Tuberc Lung Dis5:87–91.

Kazwala RR, Kusiluka LJM, Sinclair K, Sharp JM, Daborn CJ.2006. The molecular epidemiology of Mycobacterium bovisinfections in Tanzania. Vet Microbiol 112:201–210.

Am. J. Primatol.

Risk of Tuberculosis for Wild Great Apes / 11

Keele BF, Jones JH, Terio KA, et al. 2009. Increased mortalityand AIDS‐like immunopathology in wild chimpanzeesinfected with SIVcpz. Nature 460:515–519.

Keet D, Kriek N, Bengis R, Grobler D, Michel A. 2000. The riseand fall of tuberculosis in a free‐ranging chacma baboontroop in the Kruger National Park. Onderstepoort J Vet Res67:115–122.

Köndgen S, Kühl H, N’Goran PK, et al. 2008. Pandemic humanviruses cause decline of endangered great apes. Curr Biol18:260–264.

Köndgen S, Schenk S, Pauli G, Hoesch C, Leendertz F. 2010.Noninvasive monitoring of respiratory viruses in wildchimpanzees. EcoHealth 7:332–341.

Leendertz FH, Pauli G, Maetz‐Rensing K, et al. 2006.Pathogens as drivers of population declines: the importanceof systematic monitoring in great apes and other threatenedmammals. Biol Conserv 131:325–337.

Lin PL, Yee J, Klein E, Lerche NW. 2008. Immunologicalconcepts in tuberculosis diagnostics for non‐human pri-mates: a review. J Med Primatol 37:44–51.

Liu W, Worobey M, Li Y, et al. 2008. Molecular ecology andnatural history of simian foamy virus infection in wild‐livingchimpanzees. PLoS Pathog 4:e1000097.

Loomis M. 2003. Great apes. In: Fowler M, Miller R, editors.Zoo and wildlife medicine, current therapy, 5th edition. St.Louis: Saunders. p 381–396.

Lyashchenko KP, Greenwald R, Esfandiari J, et al. 2007.PrimaTB STAT‐PAK assay, a novel, rapid lateral‐flow testfor tuberculosis in nonhuman primates. Clin VaccineImmunol 14:1158–1164.

MakuwaM, Souquiere S. 2003. Occurrence of hepatitis virusesin wild‐born non‐human primates: a 3 year (1998–2001)epidemiological survey in Gabon. J Med Primatol 32:307–314.

Michel A, Huchzermeyer H. 1998. The zoonotic importance ofMycobacterium tuberculosis: transmission from human tomonkey. J S Afr Vet Med Assoc 69:64–65.

Michel A, Venter L, Espie I, Coetzee M. 2003. Mycobacteriumtuberculosis infections in eight species at the NationalZoological Gardens of South Africa, 1991–2001. J Zoo WildlMed 34:364–370.

Michel AL, Müller B, Van Helden PD. 2010. Mycobacteriumbovis at the animal‐human interface: a problem, or not? VetMicrobiol 140:371–381.

Miller M. 2008. Current diagnostic methods for tuberculosis inzoo animals. In: Fowler M, Miller R, editors. Zoo and wildanimal medicine, current therapy 6, 6th edition. St. Louis:Saunders Elsevier. p 10–19.

Mlengeya T. 2001. Respiratory disease outbreak in thechimpanzee population of Gombe National Park. TANAPAVeterinary Department Annual Report 2000/2001.

Morris RS, Pfeiffer DU, Jackson R. 1994. The epidemiology ofMycobacterium bovis infections. Vet Microbiol 40:153–177.

Mugisha L, Kücherer C, Ellerbrok H, et al. 2011. Multiple viralinfections in confiscatedwild born semi‐captive chimpanzees(Pan troglodytes schweinfurthii) in a sanctuary in Uganda:implications for sanctuary management and conservation.In: Proceedings of the American Association of Zoo Veter-inarians annual meeting. Kansas City: American Associa-tion of Zoo Veterinarians. p 190–195.

Müller‐Graf C, Collins D, Packer C, Woolhouse M. 1997.Schistosoma mansoni infection in a natural population ofolive baboons (Papio cynocephalus anubis) in Gombe StreamNational Park, Tanzania. Parasitology 115:621–627.

Murray S, Stem C, Boudreau B, Goodall J. 2000. Intestinalparasites of baboons (Papio cynocephalus anubis) andchimpanzees (Pan troglodytes) in Gombe National Park. JZoo Wildl Med 31:176–178.

Nizeyi J, Nabambejja S, Mugisha L, Majalija S, Cranfield R.2012. Risk assessment of human behaviours that mayimpact on the health of the Mountain Gorillas around

Bwindi Impenetrable National Park,WesternUganda. Afr JAnim Biomed Sci 7:102–113.

Nunn CL, Altizer S, Jones KE, Sechrest W. 2003. Comparativetests of parasite species richness in primates. Am Nat162:597–614.

NunnCL, Thrall PH, Stewart K, Harcourt AH. 2007. Emerginginfectious diseases and animal social systems. Evol Ecol22:519–543.

Oates J, Tutin C, Humle T, et al. 2008. Pan troglodytes. IUCNRed List of Threatened Species. Version 2012. 2.

Palacios G, Lowenstine L, Cranfield MR, et al. 2011. Humanmetapneumovirus infection in wild mountain gorillas,Rwanda. Emerg Infect Dis 17:711–713.

Palomino J, Leao S, Ritacco V. 2007. Tuberculosis 2007: frombasic science to patient care. Available online at: http://dspace.itg.be/handle/10390/2116 [accessed February 28,2011].

Peter J, Green C, Hoelscher M, et al. 2010. Urine for thediagnosis of tuberculosis: current approaches, clinicalapplicability, and new developments. Curr Opin Pulm Med16:262–270.

Portevin D, Gagneux S, Comas I, Young D. 2011. Humanmacrophage responses to clinical isolates from theMycobac-terium tuberculosis complex discriminate between ancientand modern lineages. PLoS Pathog 7:e1001307.

Pusey AE, Pintea L, Wilson ML, Kamenya S, Goodall J. 2007.The contribution of long‐term research at Gombe NationalPark to chimpanzee conservation. Conserv Biol 21:623–634.

Rasheed S, Zinicola R,WatsonD, Bajwa A,McDonald PJ. 2007.Intra‐abdominal and gastrointestinal tuberculosis. Colorec-tal Dis 9:773–783.

Robbins M,Williamson L. 2008.Gorilla beringei. IUCN red listof threatened species Version 2012.2.

Rudicell RS, Holland Jones J, Wroblewski EE, et al. 2010.Impact of simian immunodeficiency virus infection onchimpanzee population dynamics. PLoS Pathog 6:e1001116.

Russell DG, Barry CE, Flynn JL. 2010. Tuberculosis: what wedon’t know can, and does, hurt us. Science 328:852–856.

Rwego IB, Isabirye‐Basuta G, Gillespie TR, Goldberg TL. 2008.Gastrointestinal bacterial transmission among humans,mountain gorillas, and livestock in Bwindi ImpenetrableNational Park, Uganda. Conserv Biol 22:1600–1607.

Sandbrook C, Semple S. 2007. The rules and the reality ofmountain gorilla Gorilla beringei beringei tracking: howclose do tourists get? Oryx 40:428–433.

Sankar S, Ramamurthy M, Nandagopal B, Sridharan G. 2011.An appraisal of PCR‐based technology in the detection ofMycobacterium tuberculosis. Mol Diagn Ther 15:1–11.

Sapolsky R, Else J. 1987. Bovine tuberculosis in a wild baboonpopulation: epidemiological aspects. JMed Primatol 16:229–235.

Schaumburg F, Alabi A, Köck S, et al. 2012a. Highly divergentStaphylococcus aureus isolates from African non‐humanprimates. Environ Microbiol Rep 4:141–146.

Schaumburg F,Mugisha L, PeckB, et al. 2012b. Drug‐resistanthuman Staphylococcus aureus in sanctuary apes pose athreat to endangered wild ape populations. Am J Primatol74:1071–1075.

Schoene CUR, Brend SA. 2002. Primate sanctuaries—adelicate conservation approach. S Afr J Wildl Res 32:109–113.

Sharma M, Bhatia V. 2004. Abdominal tuberculosis. Indian JMed Res 120:305–315.

Shimada MK, Hayakawa S, Humle T, et al. 2004. Mitochon-drial DNA genealogy of chimpanzees in the Nimba moun-tains and Bossou, West Africa. Am J Primatol 64:261–275.

Sholley C. 1989. Mountain gorilla update. Oryx 23:57–58.Smiley T, Spelman L, Lukasik‐Baum M, et al. 2010. Noninva-

sive saliva collection techniques for free‐ranging mountaingorillas and captive eastern gorillas. J Zoo Wildl Med41:201–209.

Am. J. Primatol.

12 / Wolf et al.

Sreevatsan S, Pan X, Stockbauer KE, et al. 1997. Restrictedstructural gene polymorphism in the Mycobacterium tuber-culosis complex indicates evolutionarily recent globaldissemination. Proc Natl Acad Sci USA 94:9869–9874.

Tarara R, Suleman M, Sapolsky R, Wabomba M, Else J. 1985.Tuberculosis in wild olive baboons, Papio cynocephalusanubis (Lesson), in Kenya. J Wildl Dis 21:137–140.

Unwin S, Colin C, Nente C, et al. 2012. Stat‐pak® blood assaysin M. tuberculosis complex surveillance testing in popula-tions of chimpanzees (Pan sp) and orang‐utans (Pongo sp) inrange countries. In: Szentiks, Schumann, editors. 736Proceedings of the EAZWV/IZW international conferenceon diseases of zoo and wild animals. Bussolengo, Italy:European Association of Zoo and Wildlife Vets/LeibnizInstitute for Zoo and Wildlife Research, p 109.

Wallis J, Lee D., 1999. Primate conservation: the prevention ofdisease transmission. Int J Primatol 20:803–826.

Walsh P, Tutin C, Oates J, et al. 2008. Gorilla gorilla. IUCNRed List of Threatened Species. Version 2012. 2.

WCS. 2005. Consensus document outlining practical consider-ations for reducing health risks to African great apes andconservation employees through an occupational health

program. 13 p. Available online at: http://www.wcs‐ahead.org/workinggrps_greatapes.html [accessed May 16, 2013].

Whittier C. 2009. Diagnostics and epidemiology of infectiousagents in Mountain gorillas [dissertation]. Raleigh, NC:North Carolina State University. 280 p. Available online at:http://repository.lib.ncsu.edu/ir/bitstream/1840.16/6215/1/etd.pdf [accessed June 5, 2012].

WHO. 2012. Global Tuberculosis Report 2012. Geneva,Switzerland. Available online at: http://www.who.int/tb/publications/global_report/en/ [accessed February 4, 2013].

WilburAK, EngelGA,RompisAA, et al. 2012. From themouthsof monkeys: detection of Mycobacterium tuberculosis com-plex DNA from buccal swabs of synanthropic macaques. AmJ Primatol 74:676–686.

Williams J, Lonsdorf E, Wilson M, et al. 2008. Causes of deathin the Kasekela chimpanzees of Gombe National Park,Tanzania. Am J Primatol 70:766–777.

WilliamsonE,MacfieE. 2010. Best practice guidelines for greatape tourism. Gland, Switzerland: IUCN/SSC PrimateSpecialist Group. 78 p.

Woodford MH, Butynski TM, Karesh WB. 2002. Habituatingthe great apes: the disease risks. Oryx 36:153–160.

Am. J. Primatol.

Risk of Tuberculosis for Wild Great Apes / 13