Author(s): Miranda S. Bradley, MD; Carey Jackson, MD

Date Authored: March 7, 2020

Screening Prior to Immigration

Before a person may receive a Visa for immigration to the United States, they must undergo mandatory TB screening. Screening in this context typically involves a TB blood test paired with a chest radiograph (CXR). If the CXR is abnormal, a sputum sample must be taken to evaluate for acid fast bacteria.

The specific protocol for screening prior to immigration is determined by TB infection rates in the country from which they are leaving and age of the person. It is not typical for screening to take place after the person has arrived in the US as pre-departure testing is a requirement. However, it is important for physicians to remember that there are no health screening requirements for persons applying for non-immigrant Visas (eg temporary stays, foreign study, tourism), thus the important of a full history during evaluation.

When a patient is screened for tuberculosis infection there are typically two routes from which providers choose. A Mantoux Tuberculin Skin Test (TST, formerly referred to as ppd) is a common screening technique used in low risk populations that takes between 48-72 hours for results and requires patients to follow up at a second appointment within that timeline. The alternative, a TB blood test and also called interferon-gamma release assay (IGRA), is a typical lab draw. This may mean the test is more expensive than the TST and less feasible in poorly resourced areas.

Both of these techniques solely inform a provider whether or not a patient has been exposed and initially infected with the Mycobacterium tuberculosis bacteria, and not if that has led to a latent tuberculosis infection (LTBI) or TBdisease. If a person tests positive from either of the above screening tests, further testing must be conducted to determine if the bacteria has remained in the patient’s system.

TUBERCULIN SKIN TESTTB BLOOD TEST / IGRA
Tuberculin fluid injected under surface of skinRequires a facility that supports phlebotomy
Patient must return  48-72 hours post injectionTwo tests available in US: QuantiFERON Gold and T-SPOT
Positive results indicated by erythematous/edematous reaction at injection siteResults can be available in 24 hours depending on facility
If test must be repeated should be done on opposite forearmPreferred for patients who have received BCG vaccine
Preferred test for children <5yrPreferred for patients unable to return for a second appointment after TST administration
Takes 2-8 weeks post exposure for TST reaction 
False positive results may occur if patient has received BCG vaccine in the past 

Tuberculin Skin Test

The TST works by way of provoking an immune reaction at the point of injection in the skin. Screening in this manner is more common in patients who are at low risk of infection. The patient must return in 48-72 hours for injection site evaluation, and diagnosis is based on risk as well as diameter of induration (not erythema). In some cases, a 2-step TST is indicated. Healthcare workers are commonly required to have 2 step tests performed as they may have been exposed to TB more recently. The TST can only detect TB if exposure occurred >8 weeks prior to the test.  In these situations, the patient will come back at least 1 week after the first test’s results are read to have a repeat test performed.

Because the TST works by causing an immune reaction, it should be mentioned that in patients who are immunocompromised, a robust immune response may not be possible. This is a phenomenon known as anergy, and is an important reason why immunocompromised HIV + patients have a much lower threshold for a positive TST.

2004 Gabrielle Benenson

Injection of .1mL of purified protein derivative (PPD) containing 5 units of tuberculin fluid. Should be performed with a disposable 27 gauge TB syringe. The patient must return for test interpretation between 24 and 72 hours or results cannot be interpreted.

Reading a TST should be performed by a trained health care worker using a measurement aid. The diameter (in mm) of the raised area should be measured, not the area of redness. Interpretation of reaction requires knowledge of the patient’s risk of infection.

Interpreting TST

Tuberculin Blood Test

For patients who are at high risk of acquiring a TBinfection, either by way of immunocompromise or historical exposure, a TB blood test (IGRA) is the preferred route of screening. A false positive is also less likely to occur with this test if a patient has received a BCG vaccination in their lifetime.  IGRA is an ideal test with patient follow up is unlikely and you cannot depend on the patient to return in 48-72 hours after a TST.

The IGRA is not recommended for children younger than 5. Additionally, in areas of low resources, this test may have limited availability and be very expensive.

Diagnosis of Latent TB Infection

If screening tests for TB exposure are positive, the next step involves a chest radiograph to determine if there are pulmonary lesions. Lesions of the lung are the most common manifestation of TB disease, but disseminated TB can occur anywhere. If a patient has evidence of a previous TB infection on CXR, in addition to a positive TST or IGRA, they should be evaluated for TB disease by sputum culture. If multiple sputum cultures are negative for M tuberculosis bacteria, the patient should immediately begin antibiotic treatment for LTBI.

If the patient’s CXR shows a granuloma (calcified, nodular but discrete lesion without evidence of lung fibrosis), it is less likely they will incur a transformation to TB disease from LTBI. It is important to discuss with the patient the meaning of LTBI and the risk posed in times of immunocompromise.

Important Questions to Ask When Taking a Thorough History

Has anyone in your family been diagnosed with an active TB infection or latent TB infection?Exposure to TB contacts helps to determine likelihood of TB infection in your patient. This question, as well as travel history / inquiry into location of a patient’s native country are important elements of the history taking.
Have you been diagnosed with latent TB infection or TB disease in the past?In some cultures discussion of tuberculosis is very stigmatized, and a direct question such as this may be warranted. Additionally, using other words in your questioning, such has “lung disease” vs “respiratory problems” may be necessary. Please see Approach to Patients for further information regarding how to have this discussion.
Have you ever received treatment for tuberculosis infection in the past?Additionally, asking the patient if they completed the treatment or had problems adhering to the medication regimen is important. This question also informs you as to the risk the patient may have of acquiring an antibiotic resistant form of TB disease.
Have you ever been diagnosed with any other chronic medical conditions? HIV? Cancer?Determining immunocompromise status informs you of the risk the patient has of disseminated TB disease.
Are you experiencing constitutional symptoms such as fever, night sweats, weight loss, fatigue? Are you experiencing extrapulmonary TB disease symptoms such as voice hoarseness, back pain, headache, confusion or blood in the urine?This question determines the extent of the disease and further narrows TB disease on the differential. TB affecting the larynx can cause voice hoarseness, TB of the spine will cause back pain, meningitis can lead to headache and confusion, and TB affecting the kidneys may cause hematuria.

Diagnosis of TB Disease

An abnormality on CXR in a patient you suspect may have TB disease is not yet enough to make the full diagnosis. Conversely, if an abnormality is not found on CXR, but the patient’s clinical exam and symptoms lead you to suspect TB, it cannot be ruled based on a negative radiographic study alone.

Diagnosis of TB disease requires a specimen sample evaluation with smear and culture. Urine, sputum, or CSF may be used to look for Mycobacterium tuberculosis bacteria. Three separate specimens must be taken when conducting a smear sample. If acid fast bacteria are noted, the patient has an active infection of TB disease. In these cases, further testing will be done to determine drug susceptibility.

In the cases of TB disease that does not involve the lungs, a biopsy specimen should be taken of any area where TB is suspected to have invaded. After biopsy, a smear of the sample should be evaluated for acid fast bacilli for diagnosis.

Acquiring Specimens when Evaluating for Pulmonary TB Disease

  1. Coughing: Most common method, PPE required for healthcare worker, deep coughs should be encouraged to avoid samples that are diluted with saliva or mucus.
  2. Sputum Induction: Done via inhalation of warm, sterile, saline which induces deep sputum coughing.
  3. Bronchoscopy: Medical procedure that involves visualization of a patient’s lungs with a camera. Can also be used for sputum collection when previous cough attempts have failed. This form of evaluation can provide bronchial washings, brushings, and biopsy specimens.
  4. Gastric Aspiration: Medical procedure used when a patient is unable to cough the required amount of sputum for sampling. A small vacuum tube is inserted into the mouth or nose to suction up the sample.

Pulmonary TB Disease

The most common manifestation of TB disease is in the lungs. Patients will typically complain of a cough lasting for at least 3 weeks, hemoptysis, chest pain, as well as constitutional symptoms such as fever, weight loss, and fatigue. On CXR, the most common areas involved in pulmonary TB are the apical and posterior segments of the upper lobes, as well as the superior segments of the lower lobes. Patients who are HIV+ do not fit the mold, however, and may have lesions anywhere. Please refer to the Physical Manifestations of Tuberculosis Infection page for more information.

Resources

CDC Domestic Tuberculosis Guidelines
Guidelines for Screening for Tuberculosis Infection and Disease during the Domestic Medical Examination for Newly Arrived Refugees. Core Curriculum on Tuberculosis: What the Clinician Should Know
This CDC curriculum provides clinicians and other public health professionals with information on diagnosing and treating latent TB infection and TB disease. The target audience of the course is clinicians caring for people with or at high risk for TB disease. Chapter 3: Testing for Tuberculosis Infection and Disease Chapter 4: Diagnosis of Tuberculosis Disease