≥ 92% of participants will know the transmission of tuberculosis, who is at risk, the signs and symptoms, the different types, and how tuberculosis is diagnosed and treated.
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≥ 92% of participants will know the transmission of tuberculosis, who is at risk, the signs and symptoms, the different types, and how tuberculosis is diagnosed and treated.
After completing this course, the learner will be able to:
Tuberculosis (TB) is an infectious disease caused by a bacterium of the Mycobacterium (M. tuberculosis) complex (Raviglione & Gori, 2022).
A TB infection can be easily cured with prompt recognition and proper care (Raviglione & Gori, 2022). In the United States (U.S.), TB infections and death from TB are uncommon for most of the population (Centers for Disease Control and Prevention [CDC], n.d.).
Tuberculosis Infection
In the U.S., in 2024, 10,347 cases of TB were reported; this is an increase from 2022 (CDC, 2025c). An estimated 13 million Americans have latent TB (CDC, 2024d). Knowing the true number of latent TB cases is difficult because latent TB is not a reportable disease (Mirzazadeh et al., 2021). In some population groups, like non-native Americans, the prevalence of latent TB cases has been estimated to be as high as 31% (Collins et al., 2021). (Note: Latent TB will be explained later in the module.)
In the U.S., there are few TB-associated deaths. "The National Vital Statistics System collects information on reported TB disease-related deaths. Data are released after a 1-year lag. There were 565 TB-related deaths (0.2 deaths per 100,000 persons) reported in 2022" (CDC, 2024e).
M. tuberculosis is primarily transmitted by inhalation of airborne, infected droplets (Nardell, 2025b; Raviglione & Gori, 2022). The droplets are expelled by an infected person when they cough, speak, or sneeze or by any forceful respiratory effort, and after they are expelled, they become airborne (Nardell, 2025a; Raviglione & Gori, 2022). Inhaled droplets are usually expelled, but around 10% will reach the alveoli (Raviglione & Gori, 2022).
Other transmission routes, e.g., dermal transmission (Chatterjee et al., 2021), are uncommon (Raviglione & Gori, 2022). Vertical transmission of TB can happen with hematogenous (carried by the blood) transmission of the bacterium through the placenta or by aspiration of infected vaginal secretions during birth (Raviglione & Gori, 2022).
The risk of transmission and infection is primarily determined by environmental/social variables (Raviglione & Gori, 2022), like the duration of contact with an infected person, proximity to an infected person, how infectious the contacts are, and the frequency of contact with an infected person (Nardell, 2025a; Raviglione & Gori, 2022).
Approximately 5% to 10% of all people infected with TB will eventually develop active TB at some point in their lives (Nardell, 2025a; Raviglione & Gori, 2022), but the risk for any individual varies significantly (Nardell, 2025a). Factors that increase the risk of developing active TB are listed in Table 1. The common theme in these risk factors is compromised immune system function (Ali et al., 2022; Awad et al., 2019; Nardell, 2025a; Vikrant, 2019). Infection with HIV is the most important risk factor for developing active TB (Raviglione & Gori, 2022).
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(Ali et al., 2022; Awad et al., 2019; Nardell, 2025a; Vikrant, 2019) |
Once the TB bacteria reach the alveoli, one of five situations can occur:
People who have primary TB may be asymptomatic, and there are no signs seen on an X-ray of a TB infection (Fitzpatrick et al., 2023), or they may have non-specific signs and symptoms like cough, fever, and pleuritic chest pain (Raviglione & Gori, 2022). As previously mentioned, primary TB can develop into active TB, and the clinical presentation does not definitively distinguish the primary disease from the reactivation of latent TB infection (Fitzpatrick et al., 2023). See the next section for a discussion of the signs and symptoms of an active TB infection.
Latent TB reactivation is characterized by non-specific signs and symptoms, including (but not limited to) anorexia, cough, dyspnea, fever, malaise, night sweats, weakness, and weight loss (Fitzpatrick et al., 2023; Raviglione & Gori, 2022).
This section will discuss the diagnosis of primary pulmonary TB infection. Diagnosing latent TB and other forms of TB will be discussed in separate sections.
Primary TB active infection is diagnosed using the following four criteria (Fitzpatrick et al., 2023; Raviglione & Gori, 2022).
There are different laboratory tests that can be used to detect and diagnose TB (Fitzpatrick et al., 2023; Lewinsohn et al., 2017; Raviglione & Gori, 2022). They include the following:
As a part of routine primary care, all patients, adults, and children should be evaluated for the presence of risk factors for M. tuberculosis exposure or for the risk of latent TB reactivation (National Society of Tuberculosis Clinicians [NSTC], 2021; Shah & Dorman, 2021).
In the U.S., the incidence of TB in healthcare personnel is similar to the incidence of TB in the general population (Sosa et al., 2019). The CDC's and the National Tuberculosis Controllers Association's (NCTA) recommendations for TB testing in healthcare personnel are listed in Table 2.
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(Sosa et al., 2019) |
Testing for latent TB should be done if the patient has a medical condition and a social situation that significantly increases the risk of developing TB infection or latent TB reactivation (NSTC, 2021; Shah & Dorman, 2021). These medical conditions and social factors are listed in Table 3.
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(NSTC, 2021; Shah & Dorman, 2021) |
Other medical conditions increase the risk of TB infection or the risk of latent TB reactivation (NSTC, 2021; Shah & Dorman, 2021). These are considered moderate risk factors (NSTC, 2021; Shah & Dorman, 2021), and testing should be considered if one or more of these factors are present (NSTC, 2021; Shah & Dorman, 2021).
"Having one or more of these conditions without a history suggestive of TB exposure is not an independent reason for being tested…. However, testing may be indicated for other reasons—for example, infection control at a hemodialysis center or local epidemiology showing an association between a condition and TB disease" (NSTC, 2021).
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(NSTC, 2021) |
The IGRA and the TST are used to test for latent TB (Lewinsohn et al., 2017; NSTC, 2021; Shah & Dorman, 2021), but these tests cannot provide direct microbiologic evidence of a TB infection (Shah & Dorman, 2021). The IGRA and the TST detect an immune response to antigens. The TST uses an intradermal injection of purified protein derivatives (PPD) of the bacterium that acts as an antigen, and the IGRA uses synthetic peptides that resemble the M. tuberculosis protein and act as antigens. The peptides are added to a blood sample, and an immune response does or does not occur (Mazurek et al., 2010).
The IGRA assay is the preferred test, but the TST can be used (Lewinsohn et al., 2017; NSTC, 2021). There are differences between the two in terms of cost, convenience, and interpretation of the results; clinicians should know and understand them. One of the most important differences involves the TST and Bacillus Calmette-Guérin (BCG) vaccination. The BCG vaccine is a live vaccine that can prevent TB infection and is widely used in other parts of the world. A BCG vaccination can cause a false-positive TST, but this does not happen with the IGRA assay (NSTC, 2021; Shah & Dorman, 2021).
Specific IGRA tests that may be used include the QuantiFERON®-TB Gold Plus (QFT-Plus) and the T-SPOT®.TB test (T-Spot). Both tests are indirect tests that should be used in conjunction with methods such as assessing patient risk, diagnostic images, such as radiography, and other tests. Both tests are based on the cell-mediated immune response (Quest Diagnostics, 2022a; Quest Diagnostics, 2022b).
Neither the IGRA nor the TST can distinguish between latent TB and active infection (Shah & Dorman, 2021), and in addition:
For patients living with HIV, the risk of latent TB reactivation is higher than average (Keramat et al., 2020). Identifying HIV-infected patients who have TB is critically important, but using the IGRA or the TST is problematic in this situation. The IGRA and the TST depend on the patient's immune response to provide a result. In immunosuppressed patients, like a patient living with HIV, immunosuppression may result in a false negative (NSTC, 2021). Behr et al. (2021) note that the IGRA and the TST are neither 100% sensitive nor specific and "... a negative TST/IGRA test is observed in 10–40% of HIV-negative individuals with culture-confirmed pulmonary TB..." (Behr et al., 2021). In addition, the accuracy of these tests decreases as the cluster of differentiation (CD) cell count decreases (Mthembu et al., 2023; NSTC, 2021).
Every patient who is living with HIV should be tested for latent TB (NSTC, 2021). If a patient's test is negative and their CD cell count is < 200 cells/cubic millimeter (mm3), and they have a significant risk for progression, e.g., close contact with someone who has TB infection, the test should be repeated when the CD cell count is > 400 cells/mm3 (NSTC, 2021).
Simultaneous testing with an IGRA and TST increases the sensitivity of detecting infection. With dual testing, "... a positive result from either test is taken as evidence of M. tuberculosis infection" (NSTC, 2021).
If a patient has no signs and symptoms of TB, the CXR is normal, and if the IGRA or the TST is positive, the patient does not have active TB; they have latent TB (NSTC, 2021).
Drug-resistant TB is caused by M. tuberculosis organisms that antitubercular drugs cannot eliminate. Drug-resistant TB is transmitted like drug-susceptible TB and is not more infectious than drug-susceptible TB (CDC, 2024b). Drug-resistant TB is less common in the U.S. population. "In 2023, there were 15 cases of pre-extensively drug-resistant TB (pre-XDR TB) and extensively drug-resistant TB (XDR TB)" (CDC, 2024c).
Drug-resistant TB occurs in primary and secondary ways. Primary drug-resistant TB is caused by person-to-person transmission of the drug-resistant bacterium (CDC, 2024b).
Secondary drug-resistant TB occurs during the treatment of drug-resistant TB, and there are multiple reasons why this can happen (CDC, 2024b). The reasons include the following:
The risk of developing drug-resistant TB increases if the following situations occur (CDC, 2024b):
Patients with risk factors for drug-resistant TB and a positive AFB smear or a positive NAA test should be tested for drug-resistant TB (CDC, 2024b).
If the initial susceptibility test of a sputum sample confirms that the patient has a strain of M. tuberculosis that is resistant to rifampin, molecular drug-resistant testing should be done (CDC, 2024b). Molecular drug-resistant testing uses DNA sequencing to detect TB mutations resistant to the first-line and second-line antitubercular medications and drugs repurposed to treat TB (CDC, 2024f).
Multiple treatment regimens are used to treat active TB (CDC, 2024b; CDC, 2025d; Fitzpatrick et al., 2023; Nardell, 2025a). The regimens are of different durations, use specific drug combinations, and differ in dosing amounts and frequency. The appropriate regimen for a patient depends on multiple factors, such as (CDC, 2025d):
Drug regimens for TB treatment can be complex; memorizing them would be impractical and unnecessary. There are many easily accessible sources for this information, like the CDC. However, in the next section, as an example, a drug-susceptible TB drug regimen is explained.
What is practical and needed is knowing how the antitubercular drugs should be administered to achieve maximum effectiveness.
The four basic categories of TB drug regimens for active TB are:
The continuation phase is typically at least two to three times as long as the initiation phase and sometimes longer. The continuation phase is intended to kill any M. tuberculosis bacilli that remain after the initiation phase and prevent treatment failure or relapse of the disease. In some clinical situations, the continuation phase is continued past the standard cutoff point (CDC, 2024b).
Basic principles of treatment for latent TB include the following (CDC, 2024b; NSTC, 2021; Shah & Dorman, 2021):
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(NSTC, 2021) |
A CXR should be done (NCTA, 2021). The type/types of CXR that should be done – posterior-anterior only, posterior-anterior, and lateral – depend on patient characteristics (NSTC, 2021). Treatment should only be done if no radiographic findings suggest or confirm the presence of active TB (NSTC, 2021).
Baseline laboratory studies that assess the hematologic status and hepatic function should be done if the patient is at risk for hepatic impairment or an immunocompromised state (NSTC, 2021). Testing for the presence of HIV should be done if the patient's HIV status is unknown, and serologic testing for hepatitis A, B, and C should be done if there is a need (NSTC, 2021).
Evaluate the benefits and risks of treatment and determine if the patient has pre-existing medical conditions that would be a contraindication to treatment. Drug-drug interactions could occur between medications the patient is taking and antitubercular drugs. The patient's pregnancy status should be determined.
For latent TB, the CDC and the NSTC preferentially recommend short-course, rifamycin-based three- or four-month treatment regimens (NSTC, 2021).
The NSTC recommends short-course regimens that include rifampin or rifapentine; regimens that only use INH are alternatives (NSTC, 2021).
There are three preferred regimens: 3HP, 4R, and 3HR. The 3HP and 4R have the strongest recommendation, and the 3HR has a conditional recommendation because it may cause hepatic damage (NSTC, 2021).
Longer regimens of six-month or nine-month duration can be used, but they have an inferior completion rate and a higher risk of hepatotoxicity compared to the shorter duration regimens (CDC, 2024b; NSTC, 2021). The nine-month treatment regimen (INH once a day or twice a week) "... is probably more efficacious and is commonly recommended for patients who are immunosuppressed, tolerating treatment at six months, and willing to continue. No single regimen is the best choice for all patients. Each patient must be evaluated based on individual characteristics, some of which may influence the choice of regimens" (NSTC, 2021).
Treatment of a patient who is living with HIV and who has latent TB should be done with consultation with a clinician who has expertise in managing this situation (CDC, 2024b). The drug regimens that can be used to treat patients living with HIV and who have latent TB are the 3HP, 4R, 3HR, and a nine-month regimen of INH, taken once a day (CDC, 2024b; CDC, 2025b).
Drug-drug interactions between the antitubercular drugs used in these regimens and the antiretroviral medications a patient takes can be clinically significant. The issue was briefly mentioned, and clinicians should refer to the Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents with HIV for up-to-date information about antiretroviral medications and drug-drug interactions.
DOT is recommended for all HIV-positive TB patients (CDC, 2025b).
Pregnant women should be screened to determine if they have risk factors for latent TB, and they should be tested for the presence of TB only if they have risk factors (NCTA, 2021). If a patient has a positive IGRA test or TST, a medical evaluation, including a CXR, should be done. The timing of when to do a CXR varies. For details on this topic, see the NSTC's publication, "Testing, and Treatment of Latent Tuberculosis Infection in the United States: Clinical Recommendations."
For many pregnant women, treatment of latent TB can begin during the postpartum period (CDC, 2024b); this is preferable because during pregnancy and in the first two to three months of the postpartum period, there is an increased risk of drug-induced hepatoxicity (CDC, 2024b).
If a pregnant woman with latent TB has a high risk of developing active TB, drug therapy should be started immediately, even during the first trimester (CDC, 2024b).
The drug regimens that can be used for pregnant women who have latent TB include the following (CDC, 2024b; NSTC, 2021):
INH can cause peripheral neuropathy; pregnancy may increase the risk of this adverse effect, and pregnant women taking INH should take pyridoxine as a prophylactic (CDC, 2024b; Drew, 2025b; NSTC, 2021).
Breastfeeding can be done safely if the mother is taking any of the approved drug regimens (NSTC, 2021). The infant does not need pyridoxine supplementation unless the infant is being given INH (NSTC, 2021).
"Some studies have shown an increase in hepatotoxicity in the first three months postpartum in women taking INH…; however, no studies have been done on the tolerance of other regimens given in the postpartum period" (NSTC, 2021). The NCTA states that during pregnancy and in the postpartum period, laboratory monitoring of a patient's hepatic function should be considered if a patient is taking INH (NSTC, 2021).
Vaccination with BCG is recommended for children who have a negative TST and who are continually exposed to, and cannot avoid contact with, adults who are not being treated with TB, adults who are being ineffectively treated, or who have INH- or rifampin-resistant TB. Because TB is relatively uncommon in the U.S., routine BCG vaccination is not recommended (CDC, 2025a).
Vaccination with BCG is recommended on a case-by-case basis for healthcare workers in situations such as caring for a high number of patients who have INH- and rifampin-resistant TB, ongoing transmission of drug-resistant M. tuberculosis to healthcare workers, or when TB infection control techniques have not been successful (CDC, 2025a). The BCG vaccine is contraindicated in immunosuppressed patients or patients who may become so, as well as in pregnant patients (CDC, 2025a).
Note: Monitoring for adverse drug effects is discussed in this section. Adverse drug effects are discussed in more detail in the next section of the module.
Patients being treated for latent TB should be evaluated at least once a month, including the following (NSTC, 2021).
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(CDC, 2024b; NSTC, 2021) |
First-line antitubercular medications can cause many adverse effects; this module will discuss those frequently mentioned in published guidelines.
The M. tuberculosis bacterium can infect any organ system (Chatterjee et al., 2021; Nardell, 2025b; Raviglione & Gori, 2022). Extrapulmonary TB is uncommon; it has been estimated that between 17%-20% of all TB infections are extrapulmonary (Chatterjee et al., 2021).
Miliary TB, aka disseminated TB, is caused by the hematogenous spread of M. tuberculosis(Nardell, 2025a; Raviglione & Gori, 2022), and miliary TB can be caused by a new infection or reactivation of latent TB (Nardell, 2025b; Raviglione & Gori, 2022). Children less than four years of age, older adults, people who are immunocompromised or who have a medical condition like diabetes mellitus or end-stage renal disease that can impair immune system function, and people who are living with HIV have the highest risk of developing miliary TB (Nardell, 2025a). In most cases, the lungs and the bone marrow are affected by miliary TB (Nardell 2025a), but there are many other possible presentations (Ilyas et al., 2022; Nardell, 2025a; Raviglione & Gori, 2022).
The clinical presentation varies depending on the site of the infection (Nardell, 2025a; Raviglione & Gori, 2022). The diagnostic workup for extrapulmonary TB, aside from tests appropriate to the site of the infection, is the same for pulmonary TB: AFB smears of respiratory specimens and tissue specimens, CXR, NAAT, IGRA, and TST (Nardell, 2025b).
Patient education and counseling should be done before and during the treatment of TB, and education and counseling should be provided, as needed, to patients' families, caregivers, and acquaintances (Akkerman et al., 2022). Education and counseling can help patients adhere to the drug treatment regimen, identify and report adverse effects, and prevent transmission of TB (Akkerman et al., 2022).
The basic components of patient education would be essentially the same for all TB patients. However, structuring and delivering education and counseling should be done in an age-specific and gender-sensitive manner, and at the patient's preferred language and literacy level (Akkerman et al., 2022; CDC, 2025a). Education should include the following:
TB is an infectious disease caused by the M. tuberculosis bacteria. TB primarily affects the lungs but can infect and damage almost any organ. TB is the leading cause of death from infectious diseases worldwide. However, it is relatively uncommon in the U.S. TB is primarily transmitted by inhalation of infected droplets that are exhaled when an infectious person coughs, sneezes, or talks.
When infected droplets are inhaled, one of these situations can occur:
Approximately 5% to 10% of all persons infected with TB will eventually develop TB, and the risk of this is higher in patients who are immunocompromised or who have a comorbidity that negatively affects the immune system.
The signs and symptoms of TB are non-specific, e.g., cough, fatigue, fever, malaise, and productive cough.
The diagnosis of TB depends on four criteria: Patient risk factors/index of suspicion, signs/symptoms, radiographic evidence, and bacteriologic evidence. Bacteriologic evidence of TB can be obtained by an AFB smear, a TST, an IGRA test, or culturing. Culturing is the definitive proof of a TB infection.
TB infections are drug-susceptible or drug-resistant. Drug-resistant TB is caused by M. tuberculosis organisms that antitubercular drugs cannot eliminate. There are two types of drug-resistant TB, MDR-TB and XDR-TB. Drug-resistant TB is uncommon in the U.S.
All suspected and confirmed TB cases should be promptly reported to local and state public health authorities.
Patients treated for active TB do not need to be hospitalized unless certain conditions are present. Hospitalized TB patients can transmit the disease, and infection control requires using an airborne infection isolation room, standard precautions, airborne precautions, respiratory precautions, and PPE.
With prompt identification of a TB infection and proper care, TB is easily cured. Treatment of TB is done by multi-drug regimens with an initiation and a continuation phase, and depending on the patient's circumstances, the treatment regimens can last at least four months or much longer. Every effort should be made to ensure patient adherence, including DOT, and there are guidelines for handling missed doses and treatment lapses. Adherence to the drug regimen is critically important, as treatment lapses can cause TB relapse, treatment failure, and other serious consequences.
At a minimum, patients receiving drug therapy to treat TB should be evaluated monthly. Clinicians should evaluate the patient's clinical condition, determine if the patient is adhering to the treatment regimen, and look for adverse effects like hepatotoxicity, peripheral neuropathy, and visual changes.
A 45-year-old female who emigrated to the U.S. from Southeast Asia six months ago visits a primary care clinic because she has had a headache and an occasional cough for the past three days. The patient states she has no chronic medical problems. She does not smoke, abuse alcohol, or use illicit drugs. She does not take any prescription medications, and aside from the headache and cough, she has been in good health. The patient states that she has never been tested for TB. She thinks – but is not sure – that close relatives with whom she lived may have been treated for TB, and she does not know if she had been given the BCG vaccine when she was a child.
The nurse practitioner diagnosed the patient with a stress headache and said that the cough may likely be caused by mild reactive airway disease. She consults with an infectious disease specialist. The infectious disease specialist notes that the patient has been living in an area where TB is endemic, and access to antitubercular medications may be difficult. She recommends testing the patient for hepatitis B and C, HIV, and TB. A TST or IGRA can be used, but the IGRA is preferable if it is likely that the patient may not return for a TST reading within the prescribed time. In addition, a CXR, complete blood count, DST, pregnancy test, and liver function tests are performed, and the patient's visual acuity and color vision are checked.
The IGRA is positive. The CXR and liver function tests are normal, as are her color vision and visual acuity; the patient does not have hepatitis B or C or HIV and is not pregnant. The results of the DST indicate susceptibility to INH and rifampin. In addition, her headache and cough have resolved, and based on the initial testing, she does not have active TB. The infectious disease specialist was consulted again. Because of where the patient was born and had recently lived and the possibility of close contact with persons who may have had active TB, she likely has latent TB, and if so, she is at high risk for reactivation. The culture test results have yet to return, but the infectious disease physician has decided to prescribe the 3HP drug regimen. The patient is advised not to become pregnant while taking antitubercular medications. The regimen is easy to do and has a minimal risk of hepatotoxicity. The 3HP regimen includes INH and rifapentine once a week for three months. The ID physician decides that DOT should be done, and arrangements are made for DOT and other evaluation/monitoring appointments.
A 19-year-old male self-referred to an emergency room. He has had a productive cough, fever, fatigue, and night sweats for approximately two weeks. The patient has a past medical history of alcohol use disorder, IV drug use, and a chronic, untreated hepatitis C infection. In addition, he is living with HIV and is taking antiretrovirals. He lives in a homeless shelter.
The patient is admitted to the hospital and placed in a private room, and airborne, respiratory, and standard precautions are put in place.
The CXR is suggestive of but not diagnostic for a cavitary disease of TB; the results of all laboratory tests are normal except for an elevated white blood count and mildly elevated alanine transaminase. His TST result is > 10 mm (Note: He has not previously had a TST). He does not have hepatitis B. His CD4 count is > 600 cells/μL. The DST indicates that the TB bacteria are susceptible to INH and rifampin.
Because there is a high index of suspicion that the patient has active TB, and there are no contraindications to its use, the patient is started on a four-month drug regimen: An eight-week initiation phase of INH, moxifloxacin, pyrazinamide, and rifapentine, orally, taken once a day, every day, and a nine-week continuation of INH, moxifloxacin, and rifapentine, once a day every day is started. A daily dose of pyridoxine is prescribed, as well. Because the patient is on antiretrovirals, a clinical pharmacologist is consulted before beginning the TB drug therapy to determine if adjustments should be made.
It is decided to delay treatment of the hepatitis C infection. The public health department is notified of the case, and efforts are made to locate people who had contact with the patient and would be at risk for transmission of TB. The patient's condition stabilizes, two AFB smears are negative, and he is discharged to supervised living. DOT at a local health clinic is arranged.
CEUFast, Inc. is committed to furthering diversity, equity, and inclusion (DEI). While reflecting on this course content, CEUFast, Inc. would like you to consider your individual perspective and question your own biases. Remember, implicit bias is a form of bias that impacts our practice as healthcare professionals. Implicit bias occurs when we have automatic prejudices, judgments, and/or a general attitude towards a person or a group of people based on associated stereotypes we have formed over time. These automatic thoughts occur without our conscious knowledge and without our intentional desire to discriminate. The concern with implicit bias is that this can impact our actions and decisions with our workplace leadership, colleagues, and even our patients. While it is our universal goal to treat everyone equally, our implicit biases can influence our interactions, assessments, communication, prioritization, and decision-making concerning patients, which can ultimately adversely impact health outcomes. It is important to keep this in mind in order to intentionally work to self-identify our own risk areas where our implicit biases might influence our behaviors. Together, we can cease perpetuating stereotypes and remind each other to remain mindful to help avoid reacting according to biases that are contrary to our conscious beliefs and values.