- Mycobacterium bovis
- Mycobacterium bovis human infection
- Mycobacterium bovis human infection prevention
- Mycobacterium bovis human infection symptoms
- Mycobacterium bovis diagnosis
- Mycobacterium bovis treatment
Mycobacterium bovis (M. bovis) the agent of bovine tuberculosis, is another mycobacterium that can cause tuberculosis (TB) disease in humans also known as zoonotic tuberculosis 1). Mycobacterium bovis is most commonly found in cattle and other animals such as bison, elk, and deer. Mycobacterium bovis transmission is well described and occurs primarily through close contact with infected cattle or consumption of contaminated animal products such as unpasteurized milk 2). Tuberculosis cases caused by transmission of other mycobacteria from other animal reservoirs (e.g., wildlife) have been anecdotally reported 3). Globally, most cases of zoonotic tuberculosis are caused by Mycobacterium bovis, and cattle are the major reservoir 4).
According to the World Health Organization (WHO), among the estimated 10 million new cases of tuberculosis (TB) in 2017, almost 20% were extrapulmonary tuberculosis (extrapulmonary tuberculosis) 5). Furthermore, in the region with high bovine tuberculosis prevalence, Mycobacterium bovis would frequently be associated with extrapulmonary disease in humans 6). In developing countries, the exact percentage of Mycobacterium bovis in human TB (tuberculosis) cases is generally underestimated, since the species diagnosis is rarely performed, especially in extrapulmonary tuberculosis cases 7). In humans, Mycobacterium bovis causes tuberculosis disease that can affect the lungs, lymph nodes, and other parts of the body. However, as with Mycobacterium tuberculosis, not everyone infected with Mycobacterium bovis becomes sick. People who are infected but not sick have what is called latent tuberculosis infection (LTBI). People who have latent tuberculosis infection do not feel sick, do not have any symptoms, and cannot spread tuberculosis (TB) to others. However, some people with latent tuberculosis infection go on to get tuberculosis disease.
Mycobacterium bovis human infection
Mycobacterium bovis causes a relatively small proportion, less than 2%, of the total number of cases of tuberculosis disease in the United States. This accounts for less than 230 tuberculosis cases per year in the United States 8). Mycobacterium bovis transmission from cattle to people was once common in the United States. This has been greatly reduced by decades of disease control in cattle and by routine pasteurization of cow’s milk 9).
People are most commonly infected with Mycobacterium bovis by eating or drinking contaminated, unpasteurized dairy products. The pasteurization process, which destroys disease-causing organisms in milk by rapidly heating and then cooling the milk, eliminates Mycobacterium bovis from milk products.
Mycobacterium bovis infection can also occur from direct contact with a wound, such as what might occur during slaughter or hunting or by inhaling the bacteria in air exhaled by animals infected with Mycobacterium bovis. Direct transmission from animals to humans through the air is thought to be rare, but Mycobacterium bovis can be spread directly from person to person when people with the Mycobacterium bovis disease in their lungs cough or sneeze.
How do I know if I’ve been infected with Mycobacterium bovis?
Most people are at very low risk for being infected with Mycobacterium bovis. People at higher risk include individuals who work with cattle, bison, or cervids (e.g., deer or elk), or products from these animals such as hides, milk, or meat. Examples of occupations or hobbies that might put people at increased risk include ranching, dairy farming, working in a slaughterhouse or as a butcher, and hunting. People who drink raw (unpasteurized) milk or consume dairy products made from raw milk are also at greater risk. People who might be at higher risk of Mycobacterium bovis infection should talk to their healthcare providers about whether they should be regularly screened for TB infection. Screening tests include the tuberculin skin test (TST) and the interferon-gamma release assay (blood test).
Mycobacterium bovis human infection prevention
The most commonly reported source of Mycobacterium bovis infection in people is the consumption of unpasteurized dairy products. Unpasteurized dairy products, such as milk or cheese, should not be consumed: although Mycobacterium bovis infection in U.S. domestic cattle is substantially reduced compared to the past, unpasteurized dairy product consumption still carries health risks. To make sure that dairy products are pasteurized, check the label and ingredients list and make sure that the word “pasteurized” is listed. Use caution when purchasing homemade dairy products such as cheeses or products that are sold without complete labeling of the ingredients.
People at risk for contact with body fluids or tissue from a wild bison or cervid (e.g., deer or elk) into a wound, such as hunters, should promptly seek medical attention and inform their healthcare providers about the exposure to a wild animal that might carry Mycobacterium bovis.
People who spend extended periods in close contact with cattle or other animals that might carry Mycobacterium bovis, such as dairy workers, should promptly seek medical attention for any illness with symptoms of tuberculosis (TB) disease as described below and ensure that their health care providers are aware that they work in close contact with animals.
Mycobacterium bovis human infection symptoms
Not all Mycobacterium bovis infections progress to tuberculosis (TB) disease, so there might be no symptoms at all. In people, symptoms of tuberculosis disease caused by Mycobacterium bovis are similar to the symptoms of tuberculosis caused by Mycobacterium tuberculosis; this can include fever, night sweats, and weight loss. Other symptoms might occur depending on the part of the body affected by the Mycobacterium bovis disease. For example, disease in the lungs can be associated with a cough, and gastrointestinal disease can cause abdominal pain and diarrhea. If untreated, a person can die of the Mycobacterium bovis disease.
Tuberculosis signs and symptoms
Symptoms of tuberculosis disease depend on where in the body the tuberculosis bacteria are growing. Tuberculosis bacteria usually grow in the lungs (pulmonary tuberculosis). tuberculosis disease in the lungs may cause symptoms such as:
- a bad cough that lasts 3 weeks or longer
- pain in the chest
- coughing up blood or sputum (phlegm from deep inside the lungs)
Other symptoms of tuberculosis disease are:
- weakness or fatigue
- weight loss
- no appetite
- sweating at night
Symptoms of tuberculosis disease in other parts of the body depend on the area affected.
People who have latent tuberculosis infection do not feel sick, do not have any symptoms, and cannot spread tuberculosis to others.
Mycobacterium bovis diagnosis
There are two kinds of tests that are used to detect tuberculosis bacteria in the body: the tuberculosis skin test and tuberculosis blood tests. A positive tuberculosis skin test or tuberculosis blood test only tells that a person has been infected with tuberculosis bacteria. It does not tell whether the person has latent tuberculosis infection (LTBI) or has progressed to tuberculosis disease. Other tests, such as a chest x-ray and a sample of sputum, are needed to see whether the person has tuberculosis disease. If a person is found to be infected with tuberculosis bacteria, other tests are needed to see if the person has latent tuberculosis infection or tuberculosis disease.
Tuberculosis skin test
The tuberculosis skin test is also called the Mantoux tuberculin skin test. A tuberculosis skin test requires two visits with a health care provider.
On the first visit the test is placed; on the second visit the health care provider reads the test.
- The tuberculosis skin test is performed by injecting a small amount of fluid (called tuberculin) into the skin on the lower part of the arm.
- A person given the tuberculin skin test must return within 48 to 72 hours to have a trained health care worker look for a reaction on the arm.
- The result depends on the size of the raised, hard area or swelling.
Positive skin test: This means the person’s body was infected with tuberculosis bacteria. Additional tests are needed to determine if the person has latent tuberculosis infection or tuberculosis disease.
Negative skin test: This means the person’s body did not react to the test, and that latent tuberculosis infection or tuberculosis disease is not likely.
There is no problem in repeating a tuberculosis skin test. If repeated, the additional test should be placed in a different location on the body (e.g., other arm).
The tuberculosis skin test is the preferred tuberculosis test for children under the age of five.
Tuberculosis blood test
tuberculosis blood tests are also called interferon-gamma release assays or IGRAs. Two tuberculosis blood tests are approved by the U.S. Food and Drug Administration (FDA) and are available in the United States: the QuantiFERON®–tuberculosis Gold In-Tube test (QFT-GIT) and the T-SPOT®.tuberculosis test (T-Spot).
A health care provider will draw a patient’s blood and send it to a laboratory for analysis and results.
- Positive tuberculosis blood test: This means that the person has been infected with tuberculosis bacteria. Additional tests are needed to determine if the person has latent tuberculosis infection or tuberculosis disease.
- Negative tuberculosis blood test: This means that the person’s blood did not react to the test and that latent tuberculosis infection or tuberculosis disease is not likely.
Tuberculosis blood tests are the preferred tuberculosis test for:
- People who have received the tuberculosis vaccine bacille Calmette–Guérin (BCG).
- People who have a difficult time returning for a second appointment to look for a reaction to the tuberculosis skin test or Mantoux tuberculin skin test.
Testing in BCG-vaccinated persons
Many people born outside of the United States have been given a vaccine called bacille Calmette–Guérin (BCG).
People who were previously vaccinated with BCG may receive a tuberculosis skin test to test for tuberculosis infection. Vaccination with BCG may cause a false positive reaction to a tuberculosis skin test. A positive reaction to a tuberculosis skin test may be due to the BCG vaccine itself or due to infection with tuberculosis bacteria.
Tuberculosis blood tests (IGRAs), unlike the tuberculosis skin test, are not affected by prior BCG vaccination and are not expected to give a false-positive result in people who have received BCG. tuberculosis blood tests are the preferred method of tuberculosis testing for people who have received the BCG vaccine.
Testing during pregnancy
There is a greater risk to a pregnant woman and her baby if tuberculosis disease is not diagnosed and treated.
Tuberculosis skin testing is considered both valid and safe throughout pregnancy. tuberculosis blood tests also are safe to use during pregnancy, but have not been evaluated for diagnosing tuberculosis infection in pregnant women. Other tests are needed to show if a person has tuberculosis disease.
Diagnosing latent tuberculosis infection and disease
Most persons, but not everyone, with tuberculosis disease have one or more symptoms of tuberculosis disease. All persons with either symptoms or a positive tuberculosis test result should be evaluated for tuberculosis disease. If a person has symptoms, but a negative tuberculosis test result, they should still be evaluated for tuberculosis disease.
Diagnosis of latent tuberculosis Infection
A diagnosis of latent tuberculosis infection is made if a person has a positive tuberculosis test result and a medical evaluation does not indicate tuberculosis disease. The decision about treatment for latent tuberculosis infection will be based on a person’s chances of developing tuberculosis disease by considering their risk factors.
Diagnosis of tuberculosis disease
Tuberculosis disease is diagnosed by medical history, physical examination, chest x-ray, and other laboratory tests. tuberculosis disease is treated by taking several drugs as recommended by a health care provider.
Tuberculosis disease should be suspected in persons who have any of the following symptoms:
- Unexplained weight loss
- Loss of appetite
- Night sweats
If tuberculosis disease is in the lungs (pulmonary), symptoms may include:
- Coughing for longer than 3 weeks
- Hemoptysis (coughing up blood)
- Chest pain
If tuberculosis disease is in other parts of the body (extrapulmonary), symptoms will depend on the area affected.
People suspected of having tuberculosis disease should be referred for a complete medical evaluation, which will include the following:
1. Medical History
Clinicians should ask about the patient’s history of tuberculosis exposure, infection, or disease. It is also important to consider demographic factors (e.g., country of origin, age, ethnic or racial group, occupation) that may increase the patient’s risk for exposure to tuberculosis or to drug-resistant tuberculosis. Also, clinicians should determine whether the patient has medical conditions, such as HIV infection or diabetes, that increase the risk of latent tuberculosis infection progressing to tuberculosis disease.
2. Physical Examination
A physical exam can provide valuable information about the patient’s overall condition and other factors that may affect how tuberculosis is treated, such as HIV infection or other illnesses.
3. Test for tuberculosis infection
The Mantoux tuberculin skin test or the tuberculosis blood test can be used to test for Mycobacterium tuberculosis infection. Additional tests are required to confirm tuberculosis disease.
4. Chest radiograph
A posterior-anterior chest radiograph is used to detect chest abnormalities. Lesions may appear anywhere in the lungs and may differ in size, shape, density, and cavitation. These abnormalities may suggest tuberculosis, but cannot be used to definitively diagnose tuberculosis. However, a chest radiograph may be used to rule out the possibility of pulmonary tuberculosis in a person who has had a positive reaction to a tuberculin skin test or tuberculosis blood test and no symptoms of disease.
5. Diagnostic microbiology
The presence of acid-fast-bacilli (AFB) on a sputum smear or other specimen often indicates tuberculosis disease. Acid-fast microscopy is easy and quick, but it does not confirm a diagnosis of tuberculosis because some acid-fast-bacilli are not Mycobacterium bovis. Therefore, a culture is done on all initial samples to confirm the diagnosis. (However, a positive culture is not always necessary to begin or continue treatment for tuberculosis.) A positive culture for Mycobacterium bovis confirms the diagnosis of tuberculosis disease. Culture examinations should be completed on all specimens, regardless of AFB smear results. Laboratories should report positive results on smears and cultures within 24 hours by telephone or fax to the primary health care provider and to the state or local tuberculosis control program, as required by law.
6. Drug resistance
For all patients, the initial Mycobacterium tuberculosis isolate should be tested for drug resistance. It is crucial to identify drug resistance as early as possible to ensure effective treatment. Drug susceptibility patterns should be repeated for patients who do not respond adequately to treatment or who have positive culture results despite 3 months of therapy. Susceptibility results from laboratories should be promptly reported to the primary health care provider and to the state or local tuberculosis control program.
Mycobacterium bovis treatment
Mycobacterium bovis is treated similarly to Mycobacterium tuberculosis. In fact, healthcare providers might not know that a person has Mycobacterium bovis instead of Mycobacterium tuberculosis. Mycobacterium bovis is usually resistant to one of the antibiotics, pyrazinamide, typically used to treat tuberculosis disease. However, resistance to just pyrazinamide does not usually cause problems with treatment, because TB disease is treated with a combination of several antibiotics. Latent infection without disease is not treated with pyrazinamide.
Latent tuberculosis infection treatment
People with latent tuberculosis infection do not have symptoms, and they cannot spread tuberculosis bacteria to others. However, if latent tuberculosis bacteria become active in the body and multiply, the person will go from having latent tuberculosis infection to being sick with tuberculosis disease. For this reason, people with latent tuberculosis infection should be treated to prevent them from developing tuberculosis disease.
Treatment of latent tuberculosis infection is essential to controlling tuberculosis in the United States because it substantially reduces the risk that latent tuberculosis infection will progress to tuberculosis disease. In the United States, up to 13 million people may have latent tuberculosis infection. Without treatment, on average 1 in 10 people with latent tuberculosis infection will get sick with tuberculosis disease in the future. The risk is higher for people with HIV, diabetes, or other conditions that affect the immune system. More than 80% of people who get sick with tuberculosis disease in the United States each year get sick from untreated latent tuberculosis infection.
Treatment of latent tuberculosis infection should start after excluding the possibility of tuberculosis disease.
Groups who should be given high priority for latent tuberculosis infection treatment include:
- People with a positive tuberculosis blood test (interferon-gamma release assay or IGRA).
- People with a tuberculin skin test (TST) reaction of 5 or more millimeters who are:
- HIV-infected persons.
- Recent contacts to a patient with active tuberculosis disease.
- Persons with fibrotic changes on chest radiograph consistent with old tuberculosis.
- Organ transplant recipients.
- Persons who are immunosuppressed for other reasons (e.g., taking the equivalent of >15 mg/day of prednisone for 1 month or longer, taking TNF-α antagonists).
- People with a TST reaction of 10 or more millimeters who are:
- From countries where tuberculosis is common, including Mexico, the Philippines, Vietnam, India, China, Haiti, and Guatemala, or other countries with high rates of tuberculosis. (Of note, people born in Canada, Australia, New Zealand, or Western and Northern European countries are not considered at high risk for tuberculosis infection, unless they spent time in a country with a high rate of tuberculosis.)
- Injection drug users.
- Residents and employees of high-risk congregate settings (e.g., correctional facilities, nursing homes, homeless shelters, hospitals, and other health care facilities).
- Mycobacteriology laboratory personnel.
- Children under 4 years of age, or children and adolescents exposed to adults in high-risk categories.
Persons with no known risk factors for tuberculosis may be considered for treatment of latent tuberculosis infection if they have either a positive IGRA result or if their reaction to the tuberculin skin test (TST) is 15 mm or larger. However, targeted tuberculosis testing programs should only be conducted among high-risk groups. All testing activities should be accompanied by a plan for follow-up care for persons with latent tuberculosis infection or disease.
As of 2018, there are four CDC-recommended treatment regimens for latent tuberculosis infection that use isoniazid (INH), rifapentine (RPT), and/or rifampin (RIF). All the regimens are effective. Healthcare providers should prescribe the more convenient shorter regimens, when possible. Patients are more likely to complete shorter treatment regimens. Treatment must be modified if the patient is a contact of an individual with drug-resistant tuberculosis disease. Consultation with a tuberculosis expert is advised if the known source of tuberculosis infection has drug-resistant tuberculosis.
Table 1. Latent tuberculosis infection treatment regimens
|Isoniazid (INH)* and Rifapentine (RPT)†||3 months||Adults and Children aged 12 years and older:|
INH: 15 mg/kg rounded up to the nearest 50 or 100 mg; 900 mg maximum
10–14.0 kg 300 mg
14.1–25.0 kg 450 mg
25.1–32.0 kg 600 mg
32.1–49.9 kg 750 mg
≥50.0 kg 900 mg maximum
Children aged 2–11 years:
INH*: 25 mg/kg; 900 mg maximum
RPT†: as above
|Rifampin (RIF)§||4 months||Adult: 10 mg/kgChildren: 15–20 mg/kg‖|
Maximum dose: 600 mg
|Isoniazid (INH)||9 months||Adult: 5 mg/kg|
Children: 10–20 mg/kg¶
Maximum dose: 300 mg
|Adult:15 mg/kgChildren: 20–40 mg/kg¶Maximum dose: 900 mg||Twice weekly‡||76|
|6 months||Adult: 5 mg/kgChildren: Not recommendedMaximum dose: 300 mg||Daily||180|
|Adult: 15 mg/kgChildren: Not recommendedMaximum dose: 900 mg||Twice weekly‡||52|
* Isoniazid (INH) is formulated as 100 mg and 300 mg tablets.
† Rifapentine (RPT) is formulated as 150 mg tablets in blister packs that should be kept sealed until use.
‡ Intermittent regimens must be provided via directly observed therapy (DOT), that is, a health care worker observes the ingestion of medication.
§ Rifampin (rifampicin; RIF) is formulated as 150 mg and 300 mg capsules.
‖ The American Academy of Pediatrics acknowledges that some experts use RIF at 20–30 mg/kg for the daily regimen when prescribing for infants and toddlers (American Academy of Pediatrics. Tuberculosis. In: Kimberlin DW, Brady MT, Jackson MA, Long SS, eds. Red Book: 2018 Report of the Committee on Infectious Diseases. 31st ed. Itasca, IL: American Academy of Pediatrics; 2018:829–853).
¶ The American Academy of Pediatrics recommends an INH dosage of 10–15 mg/kg for the daily regimen and 20–30 mg/kg for the twice weekly regimen.[Source 10) ]
Treatment for tuberculosis disease
When tuberculosis bacteria become active (multiplying in the body) and the immune system can’t stop the bacteria from growing, this is called tuberculosis disease. tuberculosis disease will make a person sick. People with tuberculosis disease may spread the bacteria to people with whom they spend many hours.
It is very important that people who have tuberculosis disease are treated, finish the medicine, and take the drugs exactly as prescribed. If they stop taking the drugs too soon, they can become sick again; if they do not take the drugs correctly, the tuberculosis bacteria that are still alive may become resistant to those drugs. tuberculosis that is resistant to drugs is harder and more expensive to treat.
Tuberculosis disease can be treated by taking several drugs for 6 to 9 months. There are 10 drugs currently approved by the U.S. Food and Drug Administration (FDA) for treating tuberculosis. Of the approved drugs, the first-line anti-tuberculosis agents that form the core of treatment regimens are:
- isoniazid (INH)
- rifampin (RIF)
- ethambutol (EMB)
- pyrazinamide (PZA).
Tuberculosis regimens for drug-susceptible tuberculosis
Regimens for treating tuberculosis disease have an intensive phase of 2 months, followed by a continuation phase of either 4 or 7 months (total of 6 to 9 months for treatment).
Table 2. Drug susceptible tuberculosis disease treatment regimens
Footnotes: Use of once-weekly therapy with Isoniazid 900 mg and rifapentine 600 mg in the continuation phase is not generally recommended. In uncommon situations where more than once-weekly Directly Observed Therapy is difficult to achieve, once-weekly continuation phase therapy with Isoniazid 900 mg plus rifapentine 600 mg may be considered for use only in HIV uninfected persons without cavitation on chest radiography.
- a. Other combinations may be appropriate in certain circumstances; additional details are provided in the Official American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America Clinical Practice Guidelines: Treatment of Drug-Susceptible Tuberculosisexternal icon.
- b. When Directly Observed Therapy is used, drugs may be given 5 days per week and the necessary number of doses adjusted accordingly. Although there are no studies that compare 5 with 7 daily doses, extensive experience indicates this would be an effective practice. Directly Observed Therapy should be used when drugs are administered less than 7 days per week.
- c. Based on expert opinion, patients with cavitation on initial chest radiograph and positive cultures at completion of 2 months of therapy should receive a 7-month (31-week) continuation phase.
- d. Pyridoxine (vitamin B6), 25–50 mg/day, is given with Isoniazid to all persons at risk of neuropathy (e.g., pregnant women; breastfeeding infants; persons with HIV; patients with diabetes, alcoholism, malnutrition, or chronic renal failure; or patients with advanced age). For patients with peripheral neuropathy, experts recommend increasing pyridoxine dose to 100 mg/day.
- e. Alternatively, some U.S. TB control programs have administered intensive-phase regimens 5 days per week for 15 doses (3 weeks), then twice weekly for 12 doses.
Continuation Phase of Treatment
The continuation phase of treatment is given for either 4 or 7 months. The 4-month continuation phase should be used in most patients. The 7-month continuation phase is recommended only for the following groups:
- Patients with cavitary pulmonary tuberculosis caused by drug-susceptible organisms and whose sputum culture obtained at the time of completion of 2 months of treatment is positive;
- Patients whose intensive phase of treatment did not include Pyrazinamide;
- Patients with HIV who are not receiving antiretroviral treatment (ART) during tuberculosis treatment; and
- Patients being treated with once weekly Isoniazid and rifapentine and whose sputum culture obtained at the time of completion of the intensive phase is positive.
- (Note: Use of once-weekly therapy with Isoniazid 900 mg and rifapentine 600 mg in the continuation phase is not generally recommended. In uncommon situations where more than once-weekly DOT is difficult to achieve, once-weekly continuation phase therapy with Isoniazid 900 mg plus rifapentine 600 mg may be considered for use only in HIV uninfected persons without cavitation on chest radiography.)
Treatment for drug-resistant tuberculosis
Drug-resistant tuberculosis is caused by tuberculosis bacteria that are resistant to at least one first-line anti-tuberculosis drug. Multidrug-resistant tuberculosis is resistant to more than one anti-tuberculosis drug and at least isoniazid and rifampin.
Extensively drug-resistant tuberculosis is a rare type of multidrug-resistant tuberculosis that is resistant to isoniazid and rifampin, plus any fluoroquinolone and at least one of three injectable second-line drugs (i.e., amikacin, kanamycin, or capreomycin).
Treating and curing drug-resistant tuberculosis is complicated. Inappropriate management can have life-threatening results. Drug-resistant tuberculosis should be managed by or in close consultation with an expert in the disease.
Side effect associated with most commonly used anti-tuberculosis drugs
- Isoniazid- Asymptomatic elevation of Aminotransferases (10-20%), Clinical Hepatitis (0.6%), Peripheral neurotoxicity, Hypersensitivity 11).
- Rifampin- Pruritis, Nausea & Vomiting, Flulike symptoms, Hepatotoxicity, Orange discoloration of bodily fluid.
- Rifabutin- Neutropenia, Uveitis (0.01%), Polyarthralgias, Hepatotoxicity (1%)
- Rifapentine- Similar to Rifampin
- Pyrazinamide- Hepatotoxicity (1%), Nausea & Vomiting, Polyarthralgias (40%), Acute gouty arthritis, Rash and photosensitive dermatitis
- Ethambutol- Retrobulbar neuritis (18%)
One of the most important aspects of tuberculosis treatment is close follow up and monitoring for these side effects. Most of these side effects can be managed by either close monitoring or adjusting dose. In some cases, the medication needs to be discontinued and second-line therapy should be considered if other alternatives are not available.
References [ + ]
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|2.||↵||Cosivi O, Grange JM, Daborn CJ, Raviglione MC, Fujikura T, Cousins D, et al. Zoonotic tuberculosis due to Mycobacterium bovis in developing countries. Emerg Infect Dis. 1998;4:59–70. 10.3201/eid0401.980108|
|3.||↵||Murphree R, Warkentin JV, Dunn JR, Schaffner W, Jones TF. Elephant-to-human transmission of tuberculosis, 2009. Emerg Infect Dis. 2011;17:366–71. 10.3201/eid1703.101668|
|4.||↵||Ayele WY, Neill SD, Zinsstag J, Weiss MG, Pavlik I. Bovine tuberculosis: an old disease but a new threat to Africa. Int J Tuberc Lung Dis. 2004;8:924–37|
|5.||↵||World Health Organization. Global tuberculosis report 2018|
|8, 9.||↵||Tuberculosis (TB). Mycobacterium bovis (Bovine Tuberculosis) in Humans. https://www.cdc.gov/tb/publications/factsheets/general/mbovis.htm|
|10.||↵||Treatment Regimens for Latent TB Infection (LTBI). https://www.cdc.gov/tb/topic/treatment/ltbi.htm|
|11.||↵||Metushi I, Uetrecht J, Phillips E. Mechanism of isoniazid-induced hepatotoxicity: then and now. Br J Clin Pharmacol. 2016 Jun;81(6):1030-6.|