Bovine Tuberculin

The standard adult dosage for the tuberculin skin test (TST) using Bovine Tuberculin is 0.1 mL of the purified protein derivative. This volume typically contains 5 Tuberculin Units (TU). The dose is standardized to ensure that the resulting induration can be accurately compared against established diagnostic thresholds. For diagnostic purposes, the dose is always administered via the Mantoux technique, which involves a precise intradermal injection. Dosing does not vary based on body weight or age in the adult population, as the goal is to elicit a localized immune response rather than achieve a systemic therapeutic concentration.

Bovine Tuberculin is approved for use in pediatric populations, including infants. The dosage remains the same as the adult dose: 0.1 mL (5 TU) administered intradermally. Pediatric screening is a critical component of public health, especially for children who have been in close contact with individuals with active tuberculosis. Healthcare providers must exercise care during administration to ensure the injection is truly intradermal, as subcutaneous administration can lead to false-negative results.

Renal Impairment

No dosage adjustments are required for patients with renal impairment. Because the product is administered locally and systemic absorption is negligible, the clearance of the antigen is not significantly affected by kidney function.

Hepatic Impairment

No dosage adjustments are necessary for patients with hepatic impairment. The metabolism of Bovine Tuberculin proteins occurs primarily at the site of injection and through the lymphatic system, bypassing the need for hepatic processing.

Elderly Patients

While the dose remains 0.1 mL, the interpretation of the test in elderly patients may require special consideration. The immune response can wane with age (immunosenescence), potentially leading to false-negative results. In some cases, a 'two-step' testing procedure is used to 'boost' a dormant immune response, where a second test is administered 1-3 weeks after an initial negative result.

Bovine Tuberculin must be administered by a trained healthcare professional. It is not for self-administration. The following steps are typical:

1. 1Site Selection: The volar surface (inside) of the forearm is the preferred site. The area should be free of scars, tattoos, or visible veins.
2. 2Administration: The skin is cleansed, and a 26- or 27-gauge needle is inserted at a 5- to 15-degree angle with the bevel facing upward.
3. 3Wheal Formation: A successful injection will produce a pale, raised wheal approximately 6 to 10 mm in diameter. If no wheal forms, the dose was likely injected too deeply and must be repeated at another site.
4. 4Storage: Vials must be stored in the dark at 2°C to 8°C (36°F to 46°F). Exposure to light or freezing will denature the proteins and render the test inaccurate.

As Bovine Tuberculin is a one-time diagnostic test rather than a daily medication, a 'missed dose' refers to a failure to have the test site read by a professional within the required 48- to 72-hour window. If the patient does not return for a reading within 72 hours, the test is considered invalid and must be repeated. The repeat test can usually be performed immediately, but it should be administered on a different arm or at least 2 inches away from the original site.

Systemic overdose is extremely unlikely given the small volume (0.1 mL) used. However, an 'overdose' in the form of a hyper-reactive local response can occur in highly sensitized individuals. Signs of a severe local reaction include intense swelling, blistering (vesiculation), or tissue death (necrosis) at the injection site. In such cases, the area should be kept clean and dry, and the patient should be monitored for signs of systemic anaphylaxis, which requires emergency medical intervention.

> Important: Follow your healthcare provider's dosing instructions. Do not adjust your dose or attempt to interpret the skin reaction without medical guidance.

The most frequent side effects of Bovine Tuberculin are localized to the injection site and are actually expected components of a positive diagnostic reaction. These include:

• Erythema (Redness): The skin around the injection site may become red. It is important to note that redness alone does not indicate a positive test; only the hardness (induration) is measured.
• Pruritus (Itching): Many patients experience mild to moderate itching at the site. This is due to the release of histamines and other inflammatory mediators during the immune response.
• Tenderness: The site may feel sore or tender to the touch for 2 to 4 days following the injection.

• Ecchymosis (Bruising): Minor bruising may occur if a small blood vessel is nicked during the intradermal injection. This does not interfere with the test results.
• Lymphadenopathy: Swelling of the lymph nodes in the axilla (armpit) or neck may occur as the immune system processes the tuberculin proteins.
• Low-grade Fever: Some individuals may experience a transient, slight increase in body temperature as part of the systemic inflammatory response.

• Vesiculation and Ulceration: In highly sensitive individuals, the local reaction may progress to blistering or the formation of an open sore. This indicates a very strong positive reaction to the antigen.
• Necrosis: Localized tissue death at the injection site. This is rare but requires careful wound management to prevent secondary infection.
• Syncope (Fainting): Usually a vasovagal response to the needle stick rather than a reaction to the Bovine Tuberculin itself.

> Warning: Stop the procedure and call your doctor immediately or seek emergency care if you experience any of these symptoms of a systemic allergic reaction:

• Anaphylaxis: This is a life-threatening emergency characterized by a rapid heart rate, a sharp drop in blood pressure, and difficulty breathing.
• Angioedema: Severe swelling under the skin, particularly around the face, lips, tongue, or throat, which can obstruct the airway.
• Urticaria (Hives): A widespread, itchy rash that appears shortly after the injection.
• Wheezing or Bronchospasm: Sudden difficulty breathing or a whistling sound when inhaling/exhaling.

Bovine Tuberculin does not typically cause long-term side effects because it is not a chronic medication. However, in cases of severe local reactions (necrosis or deep ulceration), permanent scarring or hyperpigmentation at the injection site may occur. There is no evidence that Bovine Tuberculin causes long-term changes to the immune system or increases the risk of developing autoimmune disorders.

No FDA black box warnings are currently issued for Bovine Tuberculin. However, the manufacturer's labeling emphasizes that the product must never be administered to individuals who have previously experienced a severe necrotic reaction to tuberculin, as this can lead to significant local tissue damage.

Report any unusual symptoms or severe skin reactions to your healthcare provider immediately. If a blister or sore forms, do not cover it with a tight bandage or apply ointments unless directed by a physician.

Bovine Tuberculin is a diagnostic tool and must be handled with the same precautions as any biological product. The most critical safety consideration is the risk of a severe local or systemic allergic reaction. Healthcare facilities must be equipped with epinephrine (1:1000) and other emergency resuscitative equipment whenever Bovine Tuberculin is administered. Patients should be observed for at least 15 to 20 minutes following the injection to monitor for immediate hypersensitivity reactions.

No FDA black box warnings for Bovine Tuberculin. The product is considered safe for its intended diagnostic use when administered by trained professionals according to standardized protocols.

• Allergic Reactions / Anaphylaxis Risk: While rare, systemic hypersensitivity can occur. Patients with a known history of severe reactions to any component of the tuberculin solution (such as phenol, used as a preservative) should not receive the test.
• False-Negative Results: Several factors can suppress the immune response to Bovine Tuberculin, leading to a false-negative result. These include recent viral infections (e.g., measles, mumps, chickenpox), recent live virus vaccinations, malnutrition, or the use of immunosuppressive drugs like corticosteroids.
• False-Positive Results: Previous vaccination with BCG (Bacillus Calmette-Guérin) or infection with non-tuberculous mycobacteria (NTM) can cause a positive reaction to Bovine Tuberculin even in the absence of a Mycobacterium tuberculosis infection.
• Active Tuberculosis: Bovine Tuberculin is not used to monitor the progress of treatment for active TB, as the skin test remains positive even after successful therapy.

No routine laboratory tests (like blood counts or liver function tests) are required for the administration of Bovine Tuberculin. The primary 'monitoring' is the physical examination of the injection site 48 to 72 hours after administration. The healthcare provider must measure the diameter of the induration (not the redness) in millimeters using a standardized ruler.

Bovine Tuberculin does not typically affect the ability to drive or operate machinery. However, if a patient experiences dizziness or a vasovagal response (fainting) following the injection, they should wait until symptoms fully resolve before attempting these activities.

There are no known direct interactions between alcohol and Bovine Tuberculin. However, excessive alcohol consumption can suppress the immune system, which might theoretically interfere with the development of a robust delayed-type hypersensitivity reaction. It is generally advisable to avoid heavy drinking during the 72-hour window between injection and reading.

As Bovine Tuberculin is a single-dose diagnostic test, 'discontinuation' is not applicable in the traditional sense. Once the antigen is injected, the process cannot be stopped. If a patient decides they no longer want the test after the injection has occurred, the only course of action is to ignore the results, though the local reaction will still occur naturally.

> Important: Discuss all your medical conditions, especially any history of severe skin reactions or immune system disorders, with your healthcare provider before starting Bovine Tuberculin.

There are no absolute drug-drug contraindications that would result in a fatal interaction; however, certain combinations are clinically avoided because they render the diagnostic test useless.

• Live Virus Vaccines (e.g., MMR, Varicella, Yellow Fever): Live vaccines can temporarily suppress the body's T-cell mediated immune response. If a live vaccine is given shortly before a Bovine Tuberculin test, it may cause a false-negative result. The clinical consequence is a failure to detect a potentially dangerous tuberculosis infection. Management strategy: Administer the TST on the same day as the live vaccine, or wait 4 to 6 weeks after the vaccine before performing the TST.

• Systemic Corticosteroids (e.g., Prednisone, Dexamethasone): High doses of steroids (equivalent to ≥15 mg/day of prednisone for ≥2 weeks) significantly suppress the delayed-type hypersensitivity reaction. This can mask a positive TB infection. Management strategy: Delay the TST until steroid therapy is completed, or interpret a negative result with extreme caution.
• TNF-Alpha Inhibitors (e.g., Adalimumab, Etanercept): These medications are used for autoimmune diseases and specifically block the cytokines needed to form a tuberculin induration. Patients should be screened with Bovine Tuberculin before starting these drugs.

• Immunosuppressants (e.g., Methotrexate, Cyclosporine): These may reduce the size of the induration, potentially leading to an underestimation of the infection risk.
• Other Allergenic Extracts: If a patient is undergoing allergy skin testing simultaneously, the reactions may overlap, making interpretation difficult.

There are no documented food interactions with Bovine Tuberculin. Dietary choices do not affect the localized T-cell response required for the Mantoux test.

• Echinacea: Some studies suggest Echinacea may stimulate the immune system, which could theoretically intensify a local reaction, though this is not clinically standardized.
• High-dose Vitamin C: While generally safe, extreme doses of antioxidants could theoretically modulate inflammatory responses, but no specific restrictions are required.

Bovine Tuberculin does not interfere with standard blood chemistry or hematology tests. However, it will interfere with subsequent tuberculin skin tests if performed too frequently (the 'booster effect'). It does not interfere with the Interferon-Gamma Release Assay (IGRA) blood test if the blood is drawn at the time of the TST or shortly thereafter.

> Important: Tell your doctor about ALL medications, supplements, and herbal products you are taking, especially those that affect your immune system.

Bovine Tuberculin must NEVER be used in the following circumstances:

• Previous Severe Reaction: Any individual who has had a documented severe necrotic reaction, vesiculation (blistering), or ulceration during a prior tuberculin test is absolutely contraindicated from receiving it again. The risk of severe local tissue damage and potential systemic hypersensitivity is too high.
• Known Hypersensitivity to Components: Patients with a known allergy to phenol (the preservative) or any other inactive ingredient in the formulation must not receive the injection.
• Active Tuberculosis Diagnosis: If a patient is already confirmed to have active TB through sputum culture or other definitive means, the skin test is unnecessary and provides no diagnostic value, as the result is already known.

• Extensive Skin Conditions: Patients with widespread eczema, psoriasis, or severe burns at the site of injection (the forearm) should have the test delayed or performed on an alternative area of healthy skin. Inflammation or skin damage can make the induration impossible to measure accurately.
• Acute Viral Infections: It is often advisable to delay the test during an acute viral illness (like the flu) to avoid false-negative results due to temporary immune suppression.

Patients who are sensitive to Human Tuberculin (PPD-S) will also be sensitive to Bovine Tuberculin due to the high degree of protein homology between M. tuberculosis and M. bovis. There is also potential cross-sensitivity with the BCG vaccine, which is derived from an attenuated strain of M. bovis.

> Important: Your healthcare provider will evaluate your complete medical history, including previous skin test results, before prescribing Bovine Tuberculin.

Bovine Tuberculin is generally considered safe for use during pregnancy. According to the CDC and American Thoracic Society, pregnancy does not interfere with the TST result, and the test is not known to pose a risk to the developing fetus. There is no evidence of teratogenicity. Screening is particularly important for pregnant women in high-risk groups, as active tuberculosis poses a significant threat to both the mother and the infant. The benefits of identifying a latent TB infection far outweigh the minimal risks of the diagnostic procedure.

There are no known contraindications to using Bovine Tuberculin while breastfeeding. The tuberculoproteins are administered locally in a very small dose and do not pass into breast milk in any quantity that would affect a nursing infant. Breastfeeding mothers can safely undergo TB screening without interrupting their nursing schedule.

Bovine Tuberculin is safe and effective for use in children of all ages. In fact, the TST is a primary method for TB screening in pediatric populations. Healthcare providers should be aware that children under the age of 5 may have a higher risk of progressing from latent infection to active disease, making accurate testing and interpretation vital. In children who have received the BCG vaccine, a positive TST result may be difficult to interpret, and an IGRA blood test may be considered as an alternative in children 2 years and older.

In patients over the age of 65, the immune system's ability to react to the tuberculin antigen may diminish. This can lead to a 'false negative' where the patient is actually infected but doesn't show a reaction. To address this, a 'two-step' test is often used in long-term care facilities. If the first test is negative, a second test is given 1 to 3 weeks later. The first test 'reminds' the immune system of the antigen, and the second test provides a more accurate reading.

No special precautions are needed for patients with kidney disease. The local nature of the test means that renal clearance is not a factor in the safety or efficacy of Bovine Tuberculin.

Patients with liver disease can safely receive Bovine Tuberculin. There is no evidence that hepatic dysfunction alters the T-cell mediated response required for a successful Mantoux test.

> Important: Special populations require individualized medical assessment to ensure that diagnostic results are interpreted correctly within the context of their overall health.

Bovine Tuberculin acts as an exogenous antigen that triggers a delayed-type hypersensitivity (DTH) reaction. It specifically targets memory T-lymphocytes (CD4+ T-cells). Upon intradermal injection, the proteins are captured by Langerhans cells in the epidermis and transported to local lymph nodes. If the individual has been previously exposed to Mycobacterium bovis or M. tuberculosis, these memory T-cells recognize the antigen and migrate back to the injection site. There, they release cytokines (IFN-γ, IL-2) that increase vascular permeability and recruit macrophages, leading to the characteristic firm swelling (induration).

• Dose-Response: The standard 5 TU dose is designed to be sensitive enough to detect most infections while minimizing non-specific reactions. Higher doses (e.g., 250 TU) are rarely used because they increase the rate of false positives.
• Time to Onset: The immune response begins within hours, but the physical induration usually becomes measurable at 24 hours, peaks at 48-72 hours, and may persist for up to a week.
• Duration of Effect: The test provides a 'snapshot' of the immune status at the time of administration. It does not provide long-lasting immunity or change the patient's immune profile.

| Parameter | Value |

|---|---|

| Bioavailability | Localized (Intradermal) |

| Protein Binding | N/A (Local tissue interaction) |

| Half-life | ~24-48 hours (at injection site) |

| Tmax | 48-72 hours (for clinical effect) |

| Metabolism | Local Proteolysis |

| Excretion | Lymphatic clearance |

Bovine Tuberculin is a complex mixture of proteins, lipids, and polysaccharides derived from Mycobacterium bovis. The Purified Protein Derivative (PPD) is obtained by precipitation with trichloroacetic acid or ammonium sulfate. It is soluble in water and typically buffered with phosphates and stabilized with Tween 80 (polysorbate 80) to prevent the proteins from sticking to the glass vial or plastic syringe. The molecular weight of the active proteins ranges from 10,000 to 40,000 Daltons.

Bovine Tuberculin is classified as an Allergenic Extract and a Diagnostic Antigen. Within the FDA's Established Pharmacologic Class (EPC) system, it is grouped with other biologicals like the Live Vaccinia Virus Vaccine due to its origin from live cultures, although it contains no live organisms in its final form.