Ms. E, a 33-year-old woman born in Nigeria, presented to a U.S. employee health service for a prehire clearance. She entered the United States 2 weeks ago, and her most recent screening for tuberculosis (TB) was 4 months ago in the United Kingdom. She received the Bacille Calmette-Guérin (BCG) vaccine as a child and denied any current symptoms of pulmonary TB (no unintended weight loss, night sweats, hemoptysis, and no recent contact with anyone with active TB).
Due to her country of origin and history of receiving the BCG vaccine, Ms. E was screened with an FDA-approved commercial interferon-gamma release assay (IGRA) TB test. Her 48-hour IGRA result was positive, and she was called back to the clinic to review the results and receive a chest X-ray (posterior-anterior and lateral views). The X-ray results revealed an infiltrate in the apex of the left lung and enlarged left hilar lymph nodes. A consultation and referral were made with the local health department. Sputum samples on three separate days were collected for acid-fast bacilli (AFB); all samples were negative.
A TB disease diagnosis was made based on Ms. E's IGRA result and abnormal chest X-ray, and medication treatment was initiated (see Medication management for active TB). She was advised to practice caution with coughing, sneezing, and laughing into the air to limit the risk of transmission to others. She was permitted to start working once medication therapy was initiated. Ms. E followed up with the local health department and the employee health service for her directly observed therapy (DOT) until she completed her 40 doses.
With the resurgence of TB, it is imperative that healthcare providers have the necessary skills to manage the specialized issues of prevention, recognition, and treatment of TB. This case study demonstrates how an NP can prevent further spread of TB, treat the infection effectively, and eventually cure the disease. Ms. E was diagnosed by an employee health service NP and was transferred to the care of the local health department.
Incidence and definitions of TB
Despite declining rates of TB in the United States, TB remains a communicable disease with significant public health implications. The National Tuberculosis Surveillance System indicates that TB incidence among foreign-born persons in the United States is about 13 times the incidence among U.S.-born individuals (15.1 cases per 100,000; 6,335 cases versus 1.2 cases per 100,000; 3,201 cases in 2015).1 Eliminating TB in the United States will require persistent efforts to detect and treat latent TB infection (LTBI) and capture new cases of active TB disease early.
An estimated 11 million individuals in the United States have LTBI, with a 5% to 10% chance of developing active TB during their lifetime if left untreated.2 LTBI is the presence of Mycobacterium tuberculosis in the body without signs and symptoms or diagnostic evidence of TB disease.2 Active TB disease is defined as radiographic or bacteriologic evidence of TB with or without symptoms. Extrapulmonary TB is defined as an M. tuberculosis infection affecting organs and other parts of the body, including, but not limited to, bones and joints, genitourinary tract, lymph nodes, and the abdomen.1
Approximately 66% of all newly identified cases of TB in the United States occur among foreign-born individuals, and among foreign-born individuals in the country, those of Asian descent have the highest case counts (3,007 cases).1 Five countries of origin account for 56.6% of all new TB cases in the United States: Mexico (n = 1,250; 19.7%), the Philippines (n = 819; 12.9%), India (n = 578; 9.1%), Vietnam (n = 513; 8.1%), and China (n = 424; 6.7%).1
Most U.S.-born individuals reported with TB were either non-Hispanic Blacks (1,144 cases) or non-Hispanic Whites (991 cases).1 A variety of risk factors place an individual at risk for developing an LTBI or active TB disease (see TB risk factors). HIV remains the most potent risk factor for TB disease; however, the growing prevalence of type 2 diabetes mellitus (T2DM) in low-resourced countries is creating a greater incidence risk of TB in these locations than the combined HIV-TB infection.3 The definitive pathophysiologic mechanism of the effect of T2DM as a risk factor for TB is unknown; however, some researchers suggest a link to depressed cellular immunity and dysfunction of alveolar macrophages.3
An expedient diagnosis of active TB is critical to effective treatment and prevention of transmission. The first step in the diagnostic process includes a comprehensive medical history with a focus on important demographics (for example, county of origin) and a complete physical exam. The specific questions for individuals with suspected pulmonary TB include unintended weight loss and night sweats as well as respiratory focused questions.
The clinical presentation of TB in children, however, differs by age. Children under age 2 often present with a more severe acute illness with high rates of mortality and morbidity.4 The infection may appear as a recurrent or persistent pneumonia, and TB should be suspected when illness does not improve with conventional therapy. Presentation in adolescents is similar to adult pulmonary disease; however, adolescent infection is often highly contagious and can be linked to being a source of transmission in the community.4
The presentation of extrapulmonary TB differs depending on the area of the body affected. For example, a patient with abdominal or peritoneal involvement may present with abdominal pain, swelling, bloating, and may be jaundiced. Although evaluation would begin with common GI-related questions, the standard questions for TB screening would also need to be addressed.
Diagnosing TB: Old and new approaches
Initial screening for TB starts with a tuberculin skin test (TST); however, for those with a history of BCG (vaccine or for cancer treatment) or for patients who may not return for the TST reading, IGRA has a substantial advantage. IGRA can be conducted in a single visit and does not cause a false positive in those with a history or receiving BCG.5 In the United States, diagnosis of active TB disease still relies on a chest X-ray, bacteriology, AFB sputum smears and cultures (collected at least 8 hours apart including one early morning specimen), and mycobacterium TB culture and complex. Other bacteriologic testing (for example, susceptibility testing, nucleic acid amplification, and DNA fingerprinting or genotyping) are useful in suspected outbreaks for identification and linkage to a “source case” (for example, the original individual who spread the infection or disease).
In low resourced or developing countries, the World Health Organization (WHO) recommends the loop-mediated isothermal amplification (TB-LAMP), a manual assay that requires less than 1 hour to perform and can be read with the naked eye under UV light. Following review of the latest evidence, the WHO recommends that TB-LAMP can be used as a replacement for microscopy for the diagnosis of pulmonary TB.6
Current treatment modalities: LTBI and active TB disease
Prior to initiating any therapy, a thorough history and physical exam along with baseline liver function testing should be performed. The three goals of TB treatment (for both latent tuberculosis infection [LTBI] and active TB disease) include interruption of TB transmission, prevention of drug resistance, and cure of the patient.
In 2014, the CDC updated the LTBI treatment with simplified guidelines.7 Following three randomized control trials, the CDC determined that a 12-dose treatment using two highly effective medications was equally effective to the standard 6- to 9-month regimens when used with DOTs (see LTBI treatment regimens).8
The treatment guidelines for active disease or drug susceptible tuberculosis were updated in 2017 by the WHO Guidelines Steering Group, the Guidelines Development Group, and in 2016 by the American Thoracic Society (ATS)/CDC, and the Infectious Diseases Society of America (IDSA).9,10 While the WHO did not reiterate its “six principles” from the 2010 guidelines in the 2017 update, a review of the Who and ATS/CDC/IDSA guidelines suggests that they remain relevant for all healthcare providers need to follow.
The six principles for active TB disease of patients include: Use four drugs as the initial therapy; never treat active TB with a single drug; never add a single drug to a failing TB treatment regimen; all TB medications should be administered by DOT and dosed according to phases; pyridoxine (Vitamin B6) should be added as a daily oral dose to reduce the risk of peripheral neuropathy associated with isoniazid; consultation should be sought for special cases (drug-resistant disease, individuals diagnosed with HIV, children, and pregnant women).11 Deviations to the standard regimen are rarely indicated given the growing incidence of multidrug resistant (MDR) and extensively drug resistant (XDR) TB.
Ten drugs are currently approved for treating TB, but four anti-TB agents make up the core of the regimen: isoniazid (INH), rifampin (RIF), pyrazinamide (PZA), and ethambutol (EMB). Regimens for treatment include an initial phase of 2 months, followed by a 4- or 7-month continuation phase. Treatment completion is based on a set number of doses, not just the duration of treatment (for example, initial use of INH includes a daily dose/7 days a week for 56 doses [8 weeks]).11
TB treatment in children requires dosing medication based on weight and may require collaboration with a pediatric TB specialist. No matter what additional variables apply to the child (for example, HIV positive), the dosing guidance and maximum dosing remain the same as with adults.11,12
TB treatment is more complicated when the patient presents with MDR-TB, XDR-TB, extrapulmonary or cavitary TB, a culture-negative TB, comorbid conditions (HIV, kidney dysfunction), and/or medication intolerance. In complex cases, treatment plans should only be prescribed in consultation with a TB expert and the local or state health departments. Treatment plans for drug-resistant TB cases are much longer, require frequent regimen changes (average seven times), include multiple hospitalizations (including surgical intervention), and involve substantial case-management services.13-15
Very high rates of relapse have been reported in patients who present initially with cavitation on chest X-ray and whose sputum cultures remain positive after 2 months of treatment; it is recommended that the continuation phase in such patients be extended an additional 3 months. Extrapulmonary TB is generally treated using the same drug regimens as pulmonary TB, but the treatment is extended based upon clinical response.10,11
Management of HIV-TB and TB in a patient with the comorbidities of T2DM, kidney dysfunction, and/or end-stage renal disease is complex and requires consultation from experts in the management of both the comorbid disease and TB. Individuals with TB complicated by HIV coinfection often respond to the standard, 6-month treatment; however, complications can arise. The HIV medications, protease inhibitors, and nonnucleoside reverse transcriptase inhibitors interact with the rifamycin (RIF), potentially affecting drug selection and dosing for both TB and HIV medications.16
Treatment recommendations of HIV coinfected TB patients on antiretroviral therapy change rapidly, which requires an expert in both HIV and TB management. Although the CDC has not standardized the treatment regimens for patients with T2DM and TB, research suggests that patients with T2DM and TB have more severe TB infections requiring longer treatment and are more likely to develop MDR-TB.17 Kidney dysfunction complicates TB treatment because some anti-TB medications are cleared by the kidneys. Management may be further complicated by the removal of some anti-TB agents via hemodialysis.
Adverse reactions of treatment of TB
Brief monthly assessments for adverse reactions are important; however, repeat labs are only needed if baseline labs were abnormal or if the patient reports symptoms. During monthly assessments, providers must ensure that patients understand the treatment plan and the adverse reactions to monitor for and to report to the team. The most common serious adverse reactions that patients (both adults and children) report are associated with liver toxicity.10 GI symptoms include loss of appetite, nausea/vomiting, right upper quadrant abdominal pain/discomfort, and light colored stool.
Additional symptoms that require monitoring and reporting include a change in the quantity and color of urine, jaundice, or unexplained fever for more than 3 days. Dermatologic adverse reactions include a skin rash or pruritus; patients may also develop numbness and tingling in the arms and legs. Less commonly, flulike symptoms or unusual bleeding and/or bruising may be experienced.10
All patients treated for LTBI should receive documentation that includes diagnostic results and names, dosages, and duration of drug treatment. The documentation should be kept for all future TB testing. Providers should reeducate themselves about the signs and symptoms of TB disease and when to report to a provider. Regardless of treatment status (complete or incomplete) for LTBI, repeat chest X-rays are not indicated.10
In all cases of active disease, contact evaluation (testing and evaluation of close contacts) is important. When the index case is younger than 5 years of age, is HIV positive, has a smear-positive sputum, or MDR-TB, it is essential that the investigation include family members and other close contacts. Mothers and primary caregivers are often the “source case” of exposure when infants and children are diagnosed with active disease.18
Following 2 months of treatment for active TB, the ATS/CDC/IDSA guidelines require a repeat of the CXR and AFB sputum smears/cultures. Clinical and/or radiographic improvement following treatment for pulmonary TB is strongly suggestive of culture-negative pulmonary TB; yet, medications should continue. If clinical response is satisfactory, treatment can be discontinued after 16 weeks. Follow-up recommendations urge NPs (and other providers) to work closely with the local health department to assist with improved rates of completed treatment (for example, through internal protocols for DOT).
TB has significant public and primary healthcare implications from identification of cases to prevention of worldwide spread of the disease. The current demographic shifts in the United States and the increasing global travel of U.S.- and foreign-born individuals will require NPs to be increasingly aware of this global disease. NPs are on the frontlines of healthcare. All of our communication, assessment, and cultural competence skills will be required to identify individuals at risk for LTBI and active TB disease.
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15. Marks SM, Flood J, Seaworth B, et al Treatment practices, outcomes, and costs of multidrug-resistant and extensively drug-resistant tuberculosis
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