Tuberculosis: Diagnosis and Treatment Information for Providers

State, local and Tribal health departments (LTHDs) are responsible for ensuring that adequate and appropriate TB diagnostic and treatment services are accessed. They monitor the results of therapy and provide consultation, education, and care management for persons with suspected or confirmed active TB disease.

In collaboration with the medical provider, LTHDs provide the following services for all people with suspected or confirmed active TB disease:

• Facilitation of comprehensive TB patient evaluation, testing, and treatment
• Assistance with sputum collection for submission to the Wisconsin State Lab of Hygiene (WSLH) for diagnosis and monitoring treatment response
• Provision of antituberculosis medications; there is no charge for TB-related medications through the Wisconsin TB Dispensary for uninsured or underinsured persons
• Management of care, from diagnosis to cure
• Provision of directly observed therapy (DOT) for all clients with TB disease
• Education on TB for patients and families
• Monitoring of medication side-effects and adherence
• Management of clients with complex social and economic needs affecting adherence to the TB treatment plan

In addition, LTHDs provide the following services for individuals with TB disease:

• Facilitation of respiratory isolation for persons with infectious TB
• Identification and monitoring of contacts, including TB testing (IGRA or TST) when necessary.

A risk assessment is when a person is evaluated for TB disease for risks of infection, risks for disease progression, and symptoms. They are usually completed for people who had close contact with someone with infectious TB or who were born, lived, or traveled extensively in a TB endemic country are at highest risk for TB.

Use the Wisconsin TB Risk Assessment Questionnaire and Symptom Evaluation form, F-02314 (available in English and Spanish) to help with a risk assessment.

People should be screened and tested for TB disease if they have a persistent cough lasting three or more weeks and one or more of the following symptoms:

• Unexplained weight loss
• Fever
• Night sweats
• Fatigue
• Hemoptysis
• Laboratory tests or radiographic evidence consistent with TB

Testing for TB infection usually means performing a skin test (TST) or IGRA (QuantiFERON® or T.Spot.®TB) blood test. IGRAs are preferred, especially for persons born outside the U.S. due to higher test specificity.

People who are suspected of having active TB disease may have false negative IGRA or TST results. Additional methods of evaluation are needed to diagnose TB disease (see radiography and microbiological test sections below).

Any testing should be considered together with the patient's risk of infection. Risk for TB is very low in Wisconsin. The majority of people with TB acquire the infection outside of Wisconsin. Clinicians should be aware of populations at risk for TB in their area to help guide testing and evaluation decisions. Contact the Wisconsin TB Program at DHSWITBProgram@dhs.wisconsin.gov for additional information.

All patients with a newly confirmed positive IGRA or TST test or signs or symptoms consistent with suspected TB disease should be evaluated with a chest radiograph (chest x-ray or chest CT). Chest x-rays (CXRs) are reasonably sensitive for pulmonary TB disease.

Adding a lateral view to the posteroanterior (PA) CXR may improve sensitivity for detecting active TB in immune-compromised persons, who are more likely to have atypical radiographic presentations of active TB (Meyer 2003; Eisenberg 2009). Additional imaging to rule out active TB disease may be indicated based on clinical assessment or discussion with the radiologist. A lateral view is also recommended for children under 10 years of age.

Note that CXRs are likely to be normal in patients with extrapulmonary TB disease, so the absence of lung disease on CXR does not indicate absence of infectiousness. Oropharyngeal and laryngeal TB are highly infectious, but disease cannot be detected by plain radiograph.

People who are suspected to have pulmonary TB disease, either because of abnormal chest radiograph or TB symptom evaluation, should have sputum specimens collected and sent to the laboratory for smear, culture, and molecular testing (PCR), if indicated. A series of three specimens, at least eight hours apart with at least one being an early morning specimen, are collected to diagnose pulmonary TB, determine infectiousness and release from airborne isolation, and monitor response to treatment. People unable to spontaneously produce sputum may benefit from nebulized induction. Learn more at Sputum Collection: Spontaneously Produced, P-02380 (PDF) and Sputum Collection: Nebulized Induction, P-02381 (PDF). People for whom bronchoscopy is performed should attempt to give sputum samples after the procedure, given the increased sensitivity of post-bronchoscopy specimens (2017 Clinical Practice Guidelines: Diagnosis of Tuberculosis in Adults and Children).

People who are suspected to have extrapulmonary TB disease should have other appropriate specimen samples, such as lymph node aspirates, collected and sent to the laboratory for smear and culture. All patients with confirmed extrapulmonary TB should have sputum specimens submitted for smear and culture to help rule out pulmonary TB disease.

All people with suspected active TB disease, both pulmonary and extrapulmonary, should be reported to the patient's local health department. Clinicians are encouraged to send specimens to the Wisconsin State Laboratory of Hygiene (WSLH) where rapid full-service mycobacteriology and fee exempt TB PCR testing are available. Local health departments may be able to assist with collecting sputum from high-risk persons with suspected TB. Specimen collection kits and fee-exempt specimen transport are available by calling the WSLH customer service line at 800-862-1013.

Active TB disease is treatable. Many regimens are available, depending on the person's medical history and the drug (antibiotic) susceptibility patterns, if known.

Shown below are the preferred regimens for drug-susceptible, uncomplicated pulmonary TB disease in Wisconsin. Treatment completion is measured by number of doses completed by directly observed therapy (DOT). See current 2016 Treatment of Drug Susceptible TB Guidelines (PDF) for more detailed information.

State and LTHDs are responsible for ensuring that adequate and appropriate TB-related diagnostic and treatment services are accessed. They can assist in providing education, medication, and care management for people with latent TB infection (LTBI).

In collaboration with the medical provider, LTHDs provide the following services for all people with suspect or confirmed LTBI:

• Facilitation of LTBI evaluation, testing, and treatment
• Assistance with sputum collection for submission to the Wisconsin State Lab of Hygiene (WSLH) for ruling out active TB disease
• Provision of LTBI medications through the Wisconsin TB Dispensary for uninsured or underinsured persons and who have risk for TB disease
• Provision of directly observed therapy (DOT) for clients with LTBI on a case-by-case basis
• Education on LTBI for patients and families
• Monitoring of medication side-effects and adherence

The risk assessment for LTBI is the same as the risk assessment for TB disease. People being evaluated for LTBI should be screened for:

• Epidemiologic risk of infection
• Regulatory requirements of their occupation
• Risk of progression to TB disease

Use the Wisconsin TB Risk Assessment Questionnaire and Symptom Evaluation Form, F-02314 (available in English and Spanish) when completing a risk assessment.

People with latent TB infection is by definition asymptomatic. However, they should be evaluated for symptoms that may indicate active TB disease:

• Cough lasting more than two to three weeks
• Unexplained weight loss
• Fever
• Night sweats
• Fatigue
• Hemoptysis

People with these symptoms need additional evaluation before being treated for LTBI.

Testing for TB infection usually means performing a skin test (TST) or IGRA (QuantiFERON® or T.Spot.®TB) blood test. IGRAs are preferred, especially for people born outside the U.S. due to higher test specificity. Testing for LTBI in low-risk individuals is not recommended because of increased likelihood of false positive results. See 2017 Clinical Practice Guidelines: Diagnosis of Tuberculosis in Adults and Children. Before being diagnosed with LTBI, low-risk individuals who test positive by either IGRA or TST should have a second, confirmatory test.

Any testing should be considered together with the patient’s risk of infection. Risk for TB is very low in Wisconsin. The majority of persons with TB acquire the infection outside of Wisconsin. Clinicians should be aware of populations at risk for TB in their area to help guide testing and evaluation decisions. Contact the Wisconsin TB Program at DHSWITBProgram@dhs.wisconsin.gov for additional information.

All patients with a newly confirmed positive IGRA or TST test should be evaluated with a chest radiograph (chest x-ray or chest CT). Chest x-rays (CXRs) are reasonably sensitive for pulmonary TB disease, and the vast majority of patients with newly positive TB tests can be cleared (active TB disease ruled out) based on a normal CXR and negative symptom evaluation alone. A single posterior-anterior (PA) view is usually adequate to rule out active TB disease in asymptomatic adults without TB risk factors.

Adding a lateral view to the PA CXR may improve sensitivity for detecting active TB in immune-compromised persons, who are more likely to have atypical radiographic presentations of active TB (Meyer 2003; Eisenberg 2009). Additional imaging to rule out active TB disease may be indicated based on clinical assessment or discussion with the radiologist. A lateral view is also recommended for children under 10 years of age.

People who are being evaluated for LTBI should have sputum specimens collected and sent to the laboratory for acid fast bacilli (AFB) smear, culture, and molecular testing (PCR), if indicated, when they have an abnormal chest radiograph or TB symptom evaluation or both. A series of three specimens, at least eight hours apart with at least one being an early morning specimen, are collected to diagnose pulmonary TB, determine infectiousness and release from airborne isolation, and monitor response to treatment. People unable to spontaneously produce sputum may benefit from nebulized induction. Learn more at Sputum Collection: Spontaneously Produced, P-02380 (PDF) and Sputum Collection: Nebulized Induction, P-02381 (PDF). People for whom bronchoscopy is performed should attempt to give sputum samples after the procedure, given the increased sensitivity of post-bronchoscopy specimens (2017 Clinical Practice Guidelines: Diagnosis of Tuberculosis in Adults and Children).

Public health may be able to assist with collection of spontaneous sputum specimen collection at the client's home. Please contact the client's LTHD for more information.

LTBI treatment significantly reduces the risk of the development of TB disease and is generally considered safe. For these reasons, LTBI treatment is highly encouraged.

Latent TB infection

See the following table or view Latent Tuberculosis Infection (LTBI) Treatments, P-01181 (PDF) and the CDC Treatment for Latent TB Infection webpage for more detailed information.

Rifampin hepatoxicity is an ADR associated with elevation of Alanine Aminotransferase (ALT), and disproportionate increases in bilirubin and alkaline phosphatase. These conditions should be evaluated promptly.

Evaluate the patient for hepatitis. Hepatitis signs and symptoms include:

• Abdominal pain or tenderness
• Nausea
• Vomiting
• Loss of appetite
• Persistently dark urine
• Unexplained fever for more than three days
• Jaundice
• New unexplained fatigue

Stop all TB medications until liver enzymes return to less than two times the upper limit of normal if patient has ALT levels consistent with:

• ALT levels three times or more than the upper limit of normal in the presence of hepatitis symptoms.
• ALT levels five times or more the upper limit of normal in the absence of hepatitis symptoms.

Exclude other causes of abnormal liver tests and hepatitis:

• Hepatitis B
  • Hep B surface antigen
  • Hep B Core IgM
  • Hep B surface antibody
  • Hep B PCR/DNA of blood
• Hepatitis A (Hep A IgM)
• Excessive use of alcohol, acetaminophen, or herbal supplements
• Pregnancy testing, if applicable
• Hepatitis C (Hep C antibody)

This reintroduction protocol is for people with drug susceptible TB (DS-TB) on a four drug regimen and is most commonly used for people with drug induced hepatitis. It does not apply to restarting medications when anaphylaxis or other severe, life-threatening reactions are suspected. However, it can be applied to most adverse effects that cause full interruption of TB drugs and a need to find which medication is causing the reaction.

1. Restart rifampin (RIF) at full intended dose. Take daily for 4–5 days, recheck signs and symptoms (hepatic panel function testing) if still within normal limits (WNL), then start next drug (#2).
2. Add in isoniazid (INH). Take daily for 4–5 days, recheck signs and symptoms (hepatic panel function testing) if still WNL, then start next drug (#3). Do not restart pyrazinamide (PZA) and skip to #4 if RIF and INH were tolerated. This likely indicates PZA was causative. PZA should also not be restarted if the patient is suspected or known to have m. Bovis TB or PZA resistance TB.
3. Add in PZA. Take daily 4–5 days, recheck signs and symptoms (hepatic panel function testing) if still WNL, then start next drug (#4).
4. Add in ethambutol.

Continue regimen per CDC/ ATS Treatment Guidelines for DS-TB.

Resources and references

American Thoracic Society Statement on Hepatotoxicity of Antituberculosis Therapy (PDF)

Rashes and dermatologic reactions may be an indicator of a drug allergy causing anaphylaxis or other severe, life-threatening reactions (Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), Stevens-Johnson Syndrome). Providers should assess signs of serious reactions requiring immediate medical attention.

The patient should go to the emergency department right away for evaluation if they have a new dermatologic rash and signs and symptoms such as:

• Fever
• Mucosal involvement
• Painful rather than pruritic (itchy) skin
• Epidermal detachment or blistering (peeling, flaking)
• Organ involvement

Additionally, if the patient answers “yes” to any of the following questions, they should go to the emergency department right away for evaluation . They should not take any of their TB, LTBI, or new medications until further instructions from their provider.

• Are you having any shortness of breath or trouble breathing?
• Are your lips, eyes, eyelids, ears or face swollen?
• Is there a noise in your throat or chest when you try to breath in or out (wheezing)?
• Is the inside of your mouth sore, itchy, or red?
• Are your eyes irritated or red?
• Are you having any abdominal pain or diarrhea?
• Are there any blisters or peeling of your skin?
• Is your heart rate much faster than usual?
• Are you having irregular heart rate, feeling palpitations or skipped beats?
• Is your blood pressure much lower than usual?

After provider evaluation

If the patient was suspected of having an allergy to one to the TB medications, they will likely need a referral to a local allergist for aid in safely restarting their medications.
If the patient was not suspected of having a true allergy, and is diagnosed with a simple, non-severe derm reaction in the absence of red flags for systemic involvement or allergy, the prescribing provider may opt for dual histamine blockade using two agents:

• Cetirizine 10 mg tab twice daily for seven days, then once daily for 21 days.
• Famotidine 20 mg twice daily for seven days, then 20 mg once daily for 21 days.
  • If there is no response after several days, prescribing provider may opt for prednisone 20 mg tablet: two tabs by mouth once daily for five days.

Resources and references

• Rash-Assessment and Description Guide, Heartland National TB Center, 2022.
• Nursing Guide for Managing Side Effects to Drug-resistant TB Treatment, CITC and International Council of Nurses (ICN).
• Core Curriculum on Tuberculosis: What the Clinician Should Know, CDC, 2021.

• Self-Study Modules: A series of educational modules designed to provide information about TB in a self-study format.
• 2017 Clinical Practice Guidelines: Diagnosis of Tuberculosis in Adults and Children
• 2016 Treatment of Drug Susceptible TB guidelines (PDF)
• Other CDC guidelines: List of guidelines, covering topics from managing MDR to HIV co-infection.
• 3HP, 3HR, and 4R Medication Trackers and Patient Information Sheets from CDC (including translations)

• Mayo Clinic Center for Tuberculosis (MCCT): The designated COE for Wisconsin that provides education and support for the management of TB and LTBI.
• Curry International Tuberculosis Center: Contains clinical products available for download and ordering; contains link to Drug Resistant TB: A Survival Guide for Clinicians (third ed.).
• Southeastern National Tuberculosis Center: A COE that provides educational webinars and support for the management of TB and LTBI.
• Clinical Algorithms and Short Clinical Guides, Heartland National TB Center: An assortment of clinical resources and references from a CDC-designated Center of Excellence for TB.
• Rutgers Global TB Center: Contains an assortment of training guides and archived webinars on TB.
• Skin Test Calipers and Rulers, Southeastern National TB Center: You can order tools for reading TB skin tests here.

• Statement on four-month HPMZ Regimen for TB Disease, P-03422 (PDF): Wisconsin TB Program Statement on the four-month HPMZ Regimen for TB Disease.
• "2023 TB/LTBI Training for New Staff" (March, 30th 2023): A webinar by the Wisconsin TB Program introducing TB/LTBI concepts, reporting, and case management for clinicians.
• "TB 101" (August 24, 2021): A webinar by the Wisconsin TB Program introducing general TB/LTBI concepts for clinicians. View the recording of this TB 101 webinar.
• "TB case management and evaluation for TB disease" (September 28, 2021): A webinar presented by the Wisconsin TB Program about nurse care management for active TB disease, geared towards public health clinicians. View the recording of this TB case management webinar.
• "The TB laboratory" (PDF) (Oct. 12, 2021, Simon, reproduced with permission): A webinar presented by the Wisconsin State Laboratory of Hygiene about collecting specimens and interpreting testing for TB. Geared towards clinicians, View the recording of this TB laboratory webinar.
• Wisconsin TB Risk Assessment Questionnaire and Symptom Evaluation form, F-02314 (available in English and Spanish): A worksheet to determine a person's risk for TB infection and disease.
• Positive TST-What's next? P-02288 (PDF): A fact sheet outlining steps to take after a positive skin test result.
• Positive IGRA-What's next? P-01182 (PDF): A fact sheet outlining steps to take after a positive IGRA result.
• Nurse Case Management Checklist and Timeline, P-00467 (PDF): A guide for case management activities to be completed by nurses at local health departments.
• Latent Tuberculosis Infection (LTBI) Treatments, P-01181 (PDF): See this fact sheet for information on recommended treatment for LTBI.
• LTBI FAQ Sheet, P-02429 (PDF): Frequently asked questions about LTBI.
• Documenting LTBI in WEDSS P-02426 (PDF): A manual on how to document LTBI in WEDSS.
• TB Disease Initial Request for Medication, F-44000 (PDF): Fill out this form to request medication for active TB disease from the TB program
• TB Infection Initial Request for Medication, F-00905 (Word): Fill out this form to request medication for latent TB infection (LTBI) from the TB program
• Medication Refill Request, F-44126 (PDF): Fill out this form to request a refill on medication for active TB disease from the TB program
• See Financial Resources webpage for ways to support your patient during treatment.
• Local Public Health in Wisconsin: A link to local public health departments in Wisconsin.
• Sputum Collection: Spontaneously Produced, P-02380 (PDF): A fact sheet for nursing staff on how to collect sputum specimens.
• Sputum Collection: Nebulized Induction, P-02381 (PDF): A fact sheet for nursing staff on how to collect sputum specimens.

• TB Suspect Case Data form, F-42001 (PDF): A form for reporting suspected active cases of TB.
• Latent Tuberculosis Infection (LTBI) Confidential Case Report form, F-02265 (PDF): Use this form to report cases of LTBI to your local health department.
• Latent Tuberculosis Infection (LTBI) Follow-up form, F-44125 (PDF): Use this form to communicate and document follow-up at the end of LTBI treatment.
• Interjurisdictional Tuberculosis Notification, F-42010 (PDF): Use this form to transfer cases to another jurisdiction in Wisconsin.
• Interjurisdictional TB Notification Follow-up, F-42011 (PDF): Use this form to follow up with cases who transferred to another jurisdiction in Wisconsin during treatment.
• See Reporting and Surveillance page for more information on reporting TB in Wisconsin.