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Tuberculosis in Elephants - Frequently Asked Questions
 www.elephantcare.org/TBinfo.htm

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Why does Elephant Care International emphasize TB in elephants?
What causes TB?
What type of TB do elephants get?
How do elephants get infected with TB?
Why should we be concerned about TB in elephants?
What are the clinical signs of TB in elephants?
How is TB diagnosed in elephants?
Is the trunk wash an accurate diagnostic technique?
Why isn’t the skin test used in elephants?
Are there other tests for TB in elephants?
Is the ElephantTB-STAT-PAK® Assay an accurate test?
Is TB in elephants a new problem?
Do infected captive elephants pose a danger to wild elephants and other animals like rhinos?
Can elephants be treated for TB?
What drugs are used to treat elephants for TB?
How long does treatment last?
How are the drugs administered?
Will the elephants accept the treatment?
How do you know if elephants are getting the correct drug doses?
Are there any side effects?
Once treatment has begun, are there still dangers to others?
How much does it cost to treat an elephant for TB?
Can TB in elephants be cured?
Where can I learn more about the treatment of TB in elephants?
Do elephants with TB pose a danger to the public?
How easy is it for humans to get TB?
Where can I find more information about TB in humans?
Literature Cited
Complete list of references on TB in elephants (this takes you to a new page)

Why does Elephant Care International emphasize TB in elephants?  Tuberculosis has evolved into much more deadly drug resistant strains within the past few years.  Further, we are now seeing and identifying greater numbers of elephants with TB.  In the few well studied populations of elephants we are finding that about 13 percent of elephants have TB, or one of every eight elephants.  In human terms this would cause widespread panic and be a disastrous epidemic, yet few grasp the danger to elephants. 

Our mission is “to foster and deliver healthcare for elephants and promote the harmony and well-being of humans and elephants where they share natural environments.”  Tuberculosis affects both elephants and the people who work with elephants. 

Alarmingly, 4.3 percent of new human TB cases worldwide are now multi-drug resistant (MDR TB) (Shah 2007).  This number is likely to be low as these are reported cases and many countries cannot yet identify MDR TB.  For example, almost twenty percent of samples from 3,520 isolates of the Network of Supranational Reference Laboratories from 48 countries were MDR TB and 9.9 percent met the criteria for extensively drug resistant TB (XDR TB) (Shah 2007). More than 50 percent of drug resistant TB cases are fatal, even when treatment is administered (American Lung Association 2007). The incidence of XDR TB is increasing. In the initial reported outbreak of XDR TB, 52 of 53 patients died within three weeks (WHO 2006).

Because we are “Dedicated to the Healthcare & Conservation of Elephants” and to “Facilitating the Sharing of Elephant Data among Professionals” we feel it is our responsibility to make accurate information about TB in elephants available and to help establish surveillance and control / treatment programs in Asian elephant range countries.

What causes TB? Tuberculosis (TB) is caused by bacteria in the genus Mycobacterium. There are over 100 species of mycobacteria but the two that are of greatest concern for elephants (and humans) are M. tuberculosis and M. bovis.

What type of TB do elephants get?  The human form (M. tuberculosis) and the bovine form (M. bovis) of TB can cause infection and disease in elephants.  Sometimes M. avium (the bird form) is found but it has not been associated with disease.  Other mycobacteria that occur commonly in the environment (non-tuberculous mycobacteria) may also be found in elephant trunk wash samples. To date these have not been associated with disease with the exception of two fatal cases caused by Mycobacterium szulgai (Lacasse 2006).

How do elephants get infected with TB?  TB is spread through the air on infected droplets that are aerosolized when an infected person or animal sneezes, coughs, or in the case of an elephant, sprays.  Captive elephants can get TB by inhaling infected droplets from infected humans, cattle, or other infected elephants. Elephant to elephant transmission may occur when one elephant places it trunk inside another elephant’s mouth which is a common practice for elephants. TB organisms have also been isolated from elephant feces (Payeur 2002) and other body secretions. To date TB has not been reported in wild elephants.

Why should we be concerned about TB in elephants?  Elephants are endangered, especially Asian elephants which are far fewer in number than African elephants. TB has been diagnosed in more frequently in Asian elephants although African elephants are susceptible. This may reflect the closer association of Asian elephants with humans.  

Though found in captive elephants, TB has not yet been reported in wild elephants. However, the potential for TB transmission is present whenever animals or humans intermingle. Infection may be acquired when wild elephant bulls breed captive elephants, when grazing land is shared with domestic livestock, or when captive elephants are exposed to infected humans.

TB in captive elephants can be treated, but treatment of wild elephants is not realistically achievable.  Determining if TB is present in the wild is urgent If it is not, we must institute strategies to prevent its introduction. If TB is present in wild populations, strategies to control transmission must be implemented to mitigate the TB risk to wild populations of elephants, rhinos and other species. Assessing the TB status of captive elephants in critical areas where wild and captive populations interface is a logical and achievable first step.

A 2006 study ((Rothschild) identified tuberculous lesions in 59 of 113 mastodon (Mammut americanum) skeletons (52%) and implicated TB in the mastodon’s extinction. This startling discovery is a warning for us to act now to protect our living elephant and other susceptible species.  

Tuberculosis is also a disease of global concern for humans. The StopTB Partnership (www.STOPTB.com) has adopted the slogan “TB Anywhere Is TB Everywhere” to emphasize that we must develop strategies to control human TB worldwide. We believe that “TB Anywhere is TB Everywhere” includes controlling TB at animal-human interfaces because animals may be a reservoir for TB. These human-animal interfaces include domestic cattle and monkeys as well as elephants. 

At least one case of MDR TB has occurred in an elephant in the US.  Because MDR has increased in human populations and because we are aware of elephants that have been inadequately treated, typically with single drug therapy, we expect that drug resistant TB will be found in captive range country elephants. TB-infected elephants are a potential reservoir that could infect humans and wildlife, perhaps even with more virulent and novel forms of TB.  Dr. William Modi, Genetics Division, Zoological Society of San Diego, states; “The possibility of an epidemic exists and reciprocal transmission between humans and elephants could have devastating consequences.” (personal communication, June 2007) 

Controlling TB in elephants will benefit both elephants and humans.

What are the clinical signs of TB in elephants? As in humans, TB in elephants can be a chronic, debilitating disease. Signs may include weakness, weight loss, exercise intolerance, and coughing. Elephants may not show signs until the disease is quite advanced. Even in the absence of clinical signs, infected elephants can shed TB bacteria and infect others.

How is TB diagnosed in elephants? The current method used to diagnose TB in elephants is to culture samples obtained by a trunk wash procedure (Isaza 1999), similar to obtaining a sputum sample in humans. Sterile saline is placed in the trunk, the trunk is elevated, and the elephant is instructed to forcibly exhale into a collection device (usually a zip-lock bag). This sample is submitted to a laboratory for culture.

Is the trunk wash an accurate diagnostic technique? Barring cross-contamination or laboratory error, a positive culture is an accurate indication of TB disease.  Unfortunately, a negative culture is not always informative. As shown in more detail below, cultures from elephants actually infected with TB may negative, a dangerous situation that allows the disease to progress and exposes others (elephants, humans, or other species) to the disease.

Obtaining an adequate trunk wash sample is not easy.  Some elephants do not permit their trunk to be handled and not all can be trained to forcibly exhale. The resulting sample may be from the end of the trunk instead of from deeper in the respiratory tract as intended. Because elephants use their trunks for many purposes including eating and dust bathing, contamination of the sample is a problem.

Obtaining a proper sample is one issue but processing the sample in the laboratory can also be problematic. Culture has inherent limitations as a primary diagnostic technique. 1) Failure to isolate the organism does not rule out infection. The characteristic intermittent shedding of mycobacterial organisms provides a potential for false-negative results, allowing the disease to progress undetected. 2) Overgrowth due to contamination from trunk wash samples may compromise the reliability of culture results, especially if overgrowth is not reported. 3) Reporting time is slow. Mycobacteria are slow-growing, typically requiring 8 weeks for isolation.  Infected elephants that are shedding while culture results are pending pose a risk to other elephants and humans. 4) Culture (requiring 3 samples from each elephant) is neither practical nor affordable to screen large numbers of elephants in Asia where surveillance is urgently needed.

In a TB outbreak in Sweden, five elephants were affected. Of 189 trunk wash samples collected, only 7 were positive from the 5 elephants that were confirmed (on postmortem) to be infected with TB (Moller 2005, Moller 2006, Lewerin 2005).

Why isn’t the skin test used in elephants? The skin test (a common screening test in humans) has been evaluated and is not accurate in elephants (Mikota 2001, Lewerin 2005).

Are there other tests for TB in elephants? In August 2007 the USDA licensed the ElephantTB-STAT-PAK® Assay, a serological test that detects antibodies to TB. The ElephantTB-STAT-PAK® Assay is a screening test that can be confirmed by the Multi-Antigen Print Immuno Assay (MAPIA). This is a lab-based test performed by Chembio Diagnostic Systems, Inc (Lyaschenko 2000).

Is the ElephantTB-STAT-PAK® Assay an accurate test? No test is 100% accurate but in studies conducted to date the test had been shown to be an early predictor of TB and may be positive months to years in advance of a positive culture (Lyaschenko 2000, 2005).

Is TB in elephants a new problem? Probably not, Sanskrit documents from 2000 years ago describe a disease in elephants that is clearly TB (Iyer 1937). However, as noted above, TB today has evolved into more drug resistant strains that are more deadly than in the past. TB has also been implicated in the extinction of the mastodon (Mammut americanum). In this study 59 0f 113 mastodon skeletons (52%) had bone lesions diagnostic for TB. The authors state “Recognizing that only a portion of animals infected by infectious tuberculosis develop bone involvement, the high frequency of the pathology in M. americanum suggests that tuberculosis was not simply endemic, but actually pandemic, a hyperdisease. Pandemic tuberculosis was one of several probable factors contributing to mastodon extinction (Rothschild 2006).

Do infected captive elephants pose a danger to wild elephants and other animals like rhinos? Wherever there is intermingling of captive elephants with wild elephants, domestic livestock, or humans there is a potential for disease transmission. However with diminishing habitat and human encroachment TB poses a far greater risk to wild populations than in the past.

Can elephants be treated for TB?  A number of elephants in the U.S. have been treated. A few elephants have been treated twice.  The exact number is not known because some facilities are reluctant to share information.

What drugs are used to treat elephants for TB? The same drugs that are used in humans are also used in elephants. The main or “first line” drugs are isoniazid (INH), rifampin (RIF), ethambutol (ETH), and pyrazinamide (PZA). PZA can only be used if the causative agent is M.tb as it is not effective against M. bovis. A precise (scale) weight is essential to determine accurate drug doses.

How long does treatment last? Generally for one year. This is longer than humans are treated because we are still learning about TB in elephants.

How are the drugs administered? Isoniazid and PZA can be given orally or rectally.  Rifampin and ethambutol must be given orally.

Will the elephants accept the treatment?  Elephants must be trained to accept medications given by direct oral or rectal administration.  “Direct oral” means placing the medication in the back of the mouth so the elephant cannot spit it out. Many elephants can be conditioned to accept a bite block through which a syringe can be placed. For rectal administration, elephant feces must be removed from the rectum and the medication placed by syringe into the rectum. The training phase is very important and should be gentle to achieve the elephant’s cooperation because treatment lasts for one year and drugs are given daily.

How do you know if elephants are getting the correct drug doses? The treatment protocols used in elephants are based on drug doses known to be effective in humans. Studies have also been conducted in elephants to measure isoniazid (Maslow 2005), ethambutol (Maslow 2005), pyrazinamide (Zhu 2005) and rifampin (Peloquin 2006) blood levels. These studies indicate that therapeutic blood levels known to be effective in humans can be achieved in elephants however some elephants get sick and can’t tolerate these doses.

Are there any side effects? Yes. These are strong medications and there are potential side effects. Some elephants have developed diarrhea or have stopped eating during treatment. In these cases, stopping the drugs for a few days is usually effective. Hepatitis (inflammation of the liver) may occur and for this reason liver function is monitored during treatment. Anemia is also a possibility.

Once treatment has begun, are there still dangers to others?  Once treatment is initiated it appears that elephants (like people) stop shedding within a few weeks and are probably not infectious to other animals or people.

How much does it cost to treat an elephant for TB?  In the U.S. the cost of drugs to treat one elephant for TB for one year is ~$50,000. This does not include laboratory fees to monitor drug levels and liver function. Preliminary estimates indicate that treatment in Asia may cost less than $5000 for one elephant for one year

Can TB in elephants be cured? We lack a good method to know for sure that elephants have been cured. Xrays are used in humans to evaluate lung lesions but we cannot x-ray elephants so serial cultures are used post-treatment. There is evidence that the MAPIA™ changes with treatment and may be a method to monitor treatment response (Lyashchenko 2006). A few elephants that were treated have died and most (but not all) appear to have been free of TB when they were examined postmortem.

Where can I learn more about the treatment of TB in elephants? The Guidelines for the Control of Tuberculosis in Elephants are a good resource.  These Guidelines were developed by the Elephant TB Working Group and were first published in 1997. They were revised in 2000 and 2003 as more information became available. The Guidelines are currently being revised to reflect the availability of the ElephantTB STAT-PAK® Assay described above. Also see these links on the Elephant Care website:

Comprehensive reference list on TB in elephants
ECI Elephant TB Initiative - an extensive
downloadable PDF file
Elephant Care International: TB Initiative - Presented at the 2007 meeting of Zoos and Aquariums Committed to Conservation
TB: Implications for Elephant Management in Asia -
Presented at the 2006 meeting of the American Association of Zoo Veterinarians
India: Elephant Healthcare Project
Elephant TB Initiative - Nepal TB Research

Do elephants with TB pose a danger to humans? The greatest risk is probably to elephant handlers that have close daily contact.  In one published report (Michalak 1998), 11 of 22 handlers had positive skin tests and one handler had active TB.  Several other reports discuss the zoonotic aspects of elephant TB (Davis 2001, Maslow 1997, Montali 2001, Oh 2002).

There have been no published reports of casual public contact with elephants resulting in TB. There is always a risk of disease transmission when there is contact with an infected animal or person.  People who are immunocompromised are at greater risk.

How easy is it for humans to get TB?  Different sources will give you different answers. 

The World Health Organization (WHO) says:

“When infectious people cough, sneeze, talk or spit, they propel TB germs into the air.  A person needs only to inhale a small number of these to be infected. However, people infected with TB bacilli will not necessarily become sick with the disease.  The immune system "walls off" the TB bacilli which, protected by a thick waxy coat, can lie dormant for years.  When someone's immune system is weakened, the chances of becoming sick are greater.”  See http://www.who.int/mediacentre/factsheets/who104/en/print.html 

The U.S. Center for Disease Control says:

“To become infected, a person usually has to spend a relatively long time in a closed environment where the air was contaminated by a person with untreated tuberculosis who was coughing and who had numerous M. tuberculosis organisms (or tubercle bacilli) in secretions from the lungs or voice box (larynx).  Infection is generally transmitted through the air; therefore, there is virtually no danger of its being spread by dishes, linens, and items that are touched, or by most food products.  However, it can be transmitted through unpasteurized milk or milk products obtained from infected cattle.

 

Travelers who anticipate possible prolonged exposure to tuberculosis (e.g., those who could be expected to come in contact routinely with hospital, prison, or homeless shelter populations) should be advised to have a tuberculin skin test before leaving the United States.

 

If the reaction is negative, they should have a repeat test approximately 12 weeks after returning.  Because persons with HIV infection are more likely to have an impaired response to the tuberculin skin test, travelers who are HIV positive should be advised to inform their physicians about their HIV infection status. Travelers who anticipate repeated travel with possible prolonged exposure or an extended stay  over a period of years in an endemic country should be advised to have two-step baseline testing and, if the reaction is negative, annual screening,  including a tuberculin skin test.”  See

http://wwwn.cdc.gov/travel/yellowBookCh4-TB.aspx

Regardless of how easy it is to become infected, now that drug resistant forms of TB are proliferating, the threat of becoming infected with TB cannot be taken lightly. 

Where can I find more information about TB in humans?

CDC Health Information for International Travel 2008 – Prevention of TB

http://wwwn.cdc.gov/travel/yellowBookCh4-TB.aspx

 

World Health Organization: Tuberculosis

 http://www.who.int/topics/tuberculosis/en/

American Lung Assoc. 2007 Multidrug-Resistant Tuberculosis Fact Sheet  http://www.lungusa.org/site/pp.asp?c=dvLUK9O0E&b=35815

WHO 2006 Emergence of XDR-TB http://www.who.int/mediacentre/news/notes/2006/np23/en/index.html


If you now recognize that TB in elephants is an important threat, please consider a donation to Elephant care International to help protect the elephants and the people who work with elephants.  Donate now.


References

American Lung Assoc. 2007 Multidrug-Resistant Tuberculosis Fact Sheet http://www.lungusa.org/site/pp.asp?c=dvLUK9O0E&b=35815

Davis,M., 2001. Mycobacterium tuberculosis risk for elephant handlers and veterinarians. Appl Occup Environ Hyg 16:350-353.

Isaza,R., Ketz,C.J., 1999. A Trunk Wash Technique for the Diagnosis of Tuberculosis in Elephants. Verh. ber. Erkrg. Zootiere 39:121-124.

Iyer,A.K., 1937. Veterinary science in India, ancient and modern with special reference to tuberculosis. Agric. Livest. India 7:718-724.

Lewerin,S.S., Olsson,S.L., Eld,K., Roken,B., Ghebremichael,S., Koivula,T., Kallenius,G.,
Bolske,G., 2005. Outbreak of Mycobacterium tuberculosis infection among captive Asian elephants in a Swedish zoo. Vet Rec. 156:171-175.

Lyashchenko,K., Singh,M., Colangeli,R., Gennaro,M.L., 2000. A multi-antigen print immunoassay for the development of serological diagnosis of infectious disease. Journal of Immunological Methods 242:91-100.

Lyashchenko,K., Miller,M., Waters,W.R.. Application of MAPIA (Multiple antigen print immunoassay) and rapid lateral flow technology for tuberculosis testing of elephants. 2005 Proceedings AAZV, AAWV, AZA Nutrition Advisory Group.  64-65.

Lyashchenko,K.P., Greenwald,R., Esfandiari,J., Olsen,J.H., Ball,R., Dumonceaux,G., Dunker,F., Buckley,C., Richard,M., Murray,S., Payeur,J.B., Andersen,P., Pollock,J.M., Mikota,S., Miller,M., Sofranko,D., Waters,W.R., 2006. Tuberculosis in elephants: antibody responses to defined antigens of Mycobacterium tuberculosis, potential for early diagnosis, and monitoring of treatment. Clin Vaccine Immunol 13:722-732.

Maslow,J.. Tuberculosis and other mycobacteria as zoonoses. Proceedings American Association of Zoo Veterinarians.  110-115. 1997.

Maslow,J.N., Mikota,S.K., Zhu,M., Riddle,H., Peloquin,C.A., 2005. Pharmacokinetics of ethambutol (EMB) in elephants. J Vet Pharmacol Ther 28:321-323.

Maslow,J.N., Mikota,S.K., Zhu,M., Isaza,R., Peddie,L.R., Dunker,F., Peddie,J., Riddle,H., Peloquin,CA., 2005. Population pharmacokinetics of isoniazid in the treatment of Mycobacterium tuberculosis among Asian and African elephants (Elephas maximus and Loxodonta
africana). J Vet Pharmacol Ther. 28:1-7.

Michalak,K., Austin,C., Diesel,S., Bacon,M.J., Zimmerman,P., Maslow,J.N., 1998. Mycobacterium tuberculosis infection as a zoonotic disease: transmission between humans and elephants. Emerg Infect Dis 4:283-287.

Mikota,S.K., Peddie,L., Peddie,J., Isaza,R., Dunker,F., West,G., Lindsay,W., Larsen,R.S., Salman,M.D., Chatterjee,D., Payeur,J., Whipple,D., Thoen,C., Davis,D.S., Sedgwick,C., Montali,R., Ziccardi,M., Maslow,J., 2001. Epidemiology and diagnosis of Mycobacterium tuberculosis in captive Asian elephants (Elephas maximus). Journal of Zoo and Wildlife Medicine 32:1-16.

Moller,T., Roken,B., Petersson,L., Vitaud,C., Lyashchenko,K.. Preliminary results of a new serological test for detection of TB-infection (Mycobacterium tuberculosis) in elephants (Elephas maximus and Loxodonta africanum) - Swedish Case studies. Verh.ber.Erkrg.Zootiere. 42, 173-181. 2005.

Moller,T., Roken,B.O., Lewerin,S.S., Lyashchenko,K., 2006. The elephant Rapid Test (RT) the future diagnostic test for TB (M. tuberculosis) in elephants? Call for a validation study in Europe. Proceedings International Elephant Conservation and Research Symposium119-124.

Montali,R.J., Mikota,S.K., Cheng,L.I., 2001. Mycobacterium tuberculosis in zoo and wildlife species. Revue Scientifique et Technique Office International des Epizooties 20:291-303.

Oh,P., Granich,R., Scott,J., Sun,B., Joseph,M., Stringfield,C., Thisdell,S., Staley,J., Workman-Malcolm,D., Borenstein,L., Lehnkering,E., Ryan,P., Soukup,J., Nitta,A., Flood,J., 2002. Human exposure following Mycobacterium tuberculosis infection of multiple animal species in a Metropolitan Zoo. Emerg Infect Dis 8:1290-1293.

Payeur,J.B., Jarnagin,J.L., Marquardt,J.G., Whipple,D.L., 2002. Mycobacterial isolations in captive elephants in the United States. Ann N Y Acad Sci 969:256-258.

Peloquin,C.A., Maslow,J.N., Mikota,S.K., Forrest,A., Dunker,F., Isaza,R., Peddie,L.R., Peddie,J., Zhu,M., 2006. Dose selection and pharmacokinetics of rifampin in elephants for the treatment of tuberculosis. J Vet Pharmacol Ther. 29:1-6.

Rothschild,B.M., Laub,R., 2006. Hyperdisease in the late Pleistocene:validation of an early 20th century hypothesis. Naturwissenschaften 93:557-564.

Shah NS, Wright A, Bai G-H, Barrera L, Boulahbal F, Martín-Casabona N, et al. Worldwide emergence of extensively drug-resistant tuberculosis. Emerg Infect Dis [serial on the Internet]. 2007 Mar [date cited]. Available from http://www.cdc.gov/EID/content/13/3/380.htm

WHO 2006 Emergence of XDR-TB http://www.who.int/mediacentre/news/notes/2006/np23/en/index.html

Zhu,M., Maslow,J.N., Mikota,S.K., Isaza,R., Dunker,F., Peloquin,C.A., 2005. Population pharmacokinetics of pyrazinamide in elephants. Journal of Veterinary Pharmacology and Therapeutics 28:403-409.

Text Box: For additional information:
Comprehensive reference list on TB in elephants 
 

 

 

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