Tuberculosis (FL INITAL Autonomous practice - Differential Diagnosis)

A total of 9,029 cases of Tuberculosis (TB) were reported in the United States in 2018 (Talwar et al., 2018). This is the lowest reported number of cases on record in the United States, and the incidence of TB cases in the United States has been declining for many years. In 2017 there were 128 cases of multi-drug resistant tuberculosis (MDR-TB) in the United States and 3 cases of extensively drug-resistant TB (Talwar et al., 2018).

Unfortunately, the statistics from the rest of the world are not encouraging. Tuberculosis is the second leading cause of death from infectious disease worldwide. According to the World Health Organization (WHO), TB worldwide is one of the top 10 causes of death and the leading cause from a single infectious agent (Above HIV/AIDS) (WHO, 2020). The worldwide incidence of new cases has been steadily declining by approximately 2% a year, but the available numbers clearly remind of the disease's breadth and severity (WHO, 2020). The 2018 WHO Global report estimated that 1.7 billion people have latent TB; in 2017, there were 1.3 million deaths from TB in people who were not infected with HIV and 300,000 deaths in people with TB who were HIV infected, and; 3.5% of new cases and 18% of newly diagnosed cases had MDR-TB (WHO, 2020). The burden of the TB epidemic is predominantly in poor and developing countries. If it is treated promptly and properly, TB is curable in almost every case. However, control and cure rates are seriously affected by the lack of resources in many parts of the world, and in some countries, the fatality rate of untreated TB is 50-65% within five years of infection.

The Mycobacterium tuberculosis bacteria cause the disease of TB. The primary organs that are infected and harmed by TB are the lungs. The TB bacteria primarily gains access to the body by inhalation of infected droplets, which are spread by an infected host through coughing, sneezing, or talking. Some of the infected droplets can remain suspended in the air for several hours. Approximately 90% of inhaled TB-infected droplets are trapped in the upper airways and expelled. The 10% not expelled will eventually reach the alveoli (Raviglione, 2018).

Once the TB bacteria reach the alveoli, one of three situations occurs:

1. The patient may completely clear the bacteria, and no infection develops;
2. The patient may develop an active infection soon after transmission, and a condition called primary TB or;
3. The body's immune response to the infection may contain the TB bacteria, causing a chronic, asymptomatic sub-clinical infection called latent TB (Riley, 2018).

Tuberculosis infections, latent or primary, can be easily treated but can develop into multidrug-resistant Tuberculosis (MDR-TB) or extensively drug-resistant Tuberculosis (XDR-TB). The body's immune system can often produce enough response to clear a TB infection or contain it. However, the immune system does not produce long-lasting immunity against TB. Another infection and active disease can occur even if the bacteria from a previous infection were cleared.

Latent TB is the most common of these three possibilities (Riley, 2018). If the host has a normal immune system, the TB bacteria reach the alveoli, and macrophages contain them. Macrophages are specialized cells of the immune system that perform many functions. In the situation of a TB infection, the macrophages surround and contain TB bacteria by a process called phagocytosis. The phagocytosis of TB bacteria produces a barrier around them: a granuloma shell. Typically, when macrophages engulf bacteria or other xenobiotics, the foreign particles are eventually destroyed by enzymes inside the macrophage. However, because of the physical nature of the granuloma and the characteristics of the TB bacteria that protect it from macrophagic enzymes, TB can live inside these granulomas for many, many years.

Approximately 5-10% of people with latent TB will eventually develop the active disease; this is called reactivation and will be discussed in a separate section (Riley, 2018). Approximately 90% of all TB cases are caused by reactivation, but primary TB is much more common in areas where TB is endemic and healthcare resources are lacking.

Primary TB happens in about 5% of all cases of infection. It typically happens to children or people with a compromised immune system. Children who are < 1 year of age have approximately a 50% chance of developing primary active TB, and because of their immature immune system, infants and children are quite susceptible to developing non-pulmonary TB (Bernardo, 2018).

Tuberculosis can disseminate and cause non-pulmonary infections, especially likely in people infected with HIV. Non-pulmonary TB infections occur in 10%-40% of patients, and in descending order, the frequency of non-pulmonary TB infections is:

1. Lymph nodes
2. Pleura
3. Genito-urinary tract
4. Bones and joints
5. Meninges
6. Peritoneum
7. Pericardium (Raviglione, 2018)

With the correct medical care, primary Tuberculosis and latent TB that has been reactivated can be easily cured. However, TB infections may develop into drug-resistant Tuberculosis (DRT), either MDR-TB or XDR-TB. The risk factors for and diagnosis and treatment of these two forms of DRT will be discussed in separate sections.

Transmission of pulmonary TB occurs by inhalation of infected droplets. The bacteria can be transmitted cutaneously and by other routes, but this is quite uncommon and isolated non-pulmonary TB is not considered contagious Marais Inhalation of the infected droplets happens by being near someone who has an active infection - the host is coughing, sneezing, talking, and the infected droplets are spread into the air. The closer and more prolonged the contact, the greater the risk of transmission, and someone with TB's household contacts is very susceptible to developing the disease (Jónes-Lopez et al., 2013). Host, environmental, and bacterial factors influence the chances of transmitting TB, and the transmission process is not completely understood. Patients with active disease and a positive AFB smear (AFB smears will be discussed later) may not produce infected droplets when they cough, sneeze, etc., but the higher the concentration of bacteria in the exhaled aerosols of an infected patient, the greater the risk of transmitting TB to close contacts (Jónes-Lopez et al., 2013).

Vertical, mother-to-child transmission of Tuberculosis can occur in utero or perinatally (Newberry et al., 2018).

Tuberculosis can also be transmitted during medical procedures such as bronchoscopy, elective intubation, nebulizer treatments, and sputum induction. Latent Tuberculosis is not contagious.

The following groups are considered susceptible to the transmission of TB or developing the disease after infection with TB:

This section will discuss the diagnosis of someone with a primary pulmonary TB infection. Diagnosing latent TB, MDR-TB, and XDR-TB will be discussed in separate sections.

The signs and symptoms considered typical of TB are a cough of > two to three weeks duration, lymphadenopathy, fever, night sweats, and weight loss ((Bernardo, 2018). These are non-specific and can be caused by many infections or medical conditions, and they may be absent or relatively minor in severity if the patient is elderly or immuno-compromised.

The diagnosis of TB is made using the following four criteria (Raviglione, 2018). Of these four, the isolation and identification of Tuberculosis in sputum is the definitive, gold-standard test for diagnosing TB.

1. A high index of suspicion: Consider someone at high risk and have a high index of suspicion of the presence of TB if the patient has characteristic signs and symptoms of TB and the patient:
   1. Is infected with HIV;
   2. Has a positive TB screening test;
   3. Has been exposed to someone who is known to have an active disease;
   4. Has been treated for TB;
   5. Has traveled to an area where TB is endemic;
   6. Is homeless or incarcerated;
   7. Uses IV drugs;
   8. Is very young, or;
   9. Has other medical conditions that increase the susceptibility to the development of TB. Because the signs and symptoms of TB are non-specific and laboratory confirmation of TB takes time, the index of suspicion is the most important part of a provisional diagnosis of TB.
2. Signs and symptoms: Discussed earlier.
3. X-ray findings: A chest x-ray (CXR) is an important part of the diagnostic workup for TB. However, a chest x-ray is highly sensitive but poorly specific, and a CXR cannot distinguish between active and inactive TB and the "classic" findings of upper lobe infiltrate and cavitation may be absent (Raviglione, 2018). A chest x-ray can be suggestive of TB but not always confirmatory.
4. Laboratory testing: Laboratory testing to confirm the presence of TB can be done using an acid-fast bacillus (AFB) smear, mycobacterial culture, or testing for the presence of TB DNA. The AFB smear test is inexpensive and quick, but the sensitivity is only 40%-60% (Raviglione, 2018). Mycobacterial culture is the definitive test for TB; it is highly sensitive to the presence of TB and is also used to identify the species and to determine drug susceptibility, but the culturing, however, takes several days to complete (Bernardo, 2018). Testing for TB DNA has the advantage of quick results, high sensitivity and specificity and also determining the DNA and RNA sequences of the particular TB organism, a feature that is very helpful for tracking TB mutations and determining drug resistance (Bernardo, 2018).

Three sputum samples should be obtained. There should be an 8-24 hour interval between the collections of specimens, a minimum of 5 mL is required, and at least one specimen should be obtained in the early morning (Bernardo, 2018). If the patient is not able to produce an adequate specimen by coughing, production of a cough and sputum collection can be done by induction. A hypertonic saline solution (Usually 3-7%) is administered via nebulization; depending on the strength of the saline, the patient will inhale the solution for 20-60 minutes. The induction will usually initiate coughing and, hopefully, the production of a sputum sample. There does not appear to be a significant advantage of self-produced versus induced sputum samples for diagnosing TB (Bernardo, 2018). Care should be taken to label specimens as induced because they are often thin and watery and could mistakenly be discarded.

Bronchoscopy with lavage can be used to obtain a sputum sample. This method of obtaining sputum samples for the diagnosis of TB has a high sensitivity. However, it is costly, invasive, and time-consuming, and it should only be used if the patient cannot produce sputum by coughing or induction if the smear is negative, but there is a high index of suspicion for the presence of TB or if there is an immediate need for a diagnosis (Bernardo, 2018).

There is a classification system for a patient history of TB (CDC, 2017)

Healthcare facilities should have administrative controls and environmental controls in place to prevent the transmission of TB. The administrative controls involve issues such as staff education, reporting requirements, and risk assessments. Environmental controls are controlling the source of the infection and the environment to prevent the spread of TB. A detailed discussion of these administrative and environmental controls is available on the CDC website (CDC, 2019).

Patients who are initially suspected of having active TB should be placed in an airborne infection isolation room (CDC, 2019). If this is not immediately possible, the patient should be placed in an enclosed area away from immunocompromised patients, and the patient should wear a surgical mask. The patient should be instructed about respiratory and cough etiquette. All staff members providing patient care should wear respiratory protection, and the N95 respirator is an appropriate and common choice (CDC, 2019). Visitors should wear an N95, as well.

Once the patient is in an airborne infection isolation room, the patient no longer needs to wear a surgical mask, but respiratory and cough etiquette should be maintained. Staff entering the room should wear an N95 respirator. If the patient needs to leave the room for a procedure or testing, he/she should wear a surgical mask, not an N95 respirator. The former is designed to trap exhaled infected droplets in the mask: and the latter is designed to filter air before it is inhaled.

The N95 must be individually fitted and properly used. It is disposable and cannot be cleaned, and a seal test should be done each time an N95 is put on (Benson, 2013). Standard and airborne precautions should be observed.

Isolation can be discontinued when:

1. Three sputum samples from three consecutive days are AFB negative;
2. The patient is on the appropriate therapy, and;
3. The patient is clinically improving (Bernardo, 2018).

Someone with AFB smear-positive TB is considered to have been contagious for three months prior to the first positive smear or the onset of symptoms, whichever is earlier.8 If the AFB smear is positive, the patient has signs/symptoms consistent with TB, or a chest x-ray shows cavitation, a contact investigation should be initiated. Healthcare workers who have had contact with an infected patient and do not have documented evidence of latent TB or prior TB should be screened for TB (Sosa et al., 2019).

Tuberculosis is a reportable disease. Notifying the local health department about a confirmed case of TB is mandatory and should be done as soon as possible via telephone. Physicians are primarily responsible for reporting TB cases, but other healthcare personnel and professionals (e.g., laboratory personnel, school nurses) can notify the health department. Once the notification has been made, the patient will be interviewed, and patient contacts will be located and interviewed. Household contact with someone who has TB, particularly MDR-TB, is a significant risk for developing latent TB (Dayal et al., 2018). Martinez et al. found that children exposed to a household contact who had TB were 3.79 times more likely to have TB than unexposed children (Martinez et al., 2017). In the United States (A country with a low incidence of TB), healthcare workers have a very low risk of contracting TB from patient contact, the risk estimated to be < 0.3% (Sosa et al., 2019).

The following recommendations are from the CDC (CDC, 2017):

Patients suspected or confirmed to have TB disease are frequently sent home after starting treatment, even though they may still be infectious. Patients with TB disease can be sent home even if they do not have three negative sputum smears if the following criteria are met:

• A follow-up plan has been made with the local TB program;
• The patient is on standard TB treatment, and directly observed therapy (DOT) has been arranged;
• No infants or children less than 4 years of age or persons who are immunocompromised are present in the household;
• All household members, who are not immunocompromised, have been previously exposed to the person with TB; and
• The patient is willing to not travel outside his/her home until he/she has negative sputum smear results.

If all the above criteria are met, patients with TB disease can go home. Additionally, they are more likely to have already transmitted TB to members of their household before their TB was diagnosed and treatment was started. However, TB patients and members of their households should still take steps to prevent the spread of TB in their homes. For example, patients with TB should be instructed to cover their mouth and nose with a tissue when coughing or sneezing. Infectious TB patients should sleep alone, not in a room with other household members. Furthermore, TB patients should be advised not to have visitors until they are non-infectious.

Patients with infectious TB should not be allowed to return home where they may be exposed to a person at high risk for progressing to TB disease if infected (for example, persons who are infected with HIV or infants and children younger than age 4). Healthcare workers in home-based health care or outreach settings should be trained in detecting the signs and symptoms of TB disease. Training should include the role of the health care worker in educating patients about the importance of reporting symptoms or signs. Health care workers should also educate patients and other household members about the importance of taking medications as prescribed.

Health care workers should not perform cough-inducing or aerosol-generating procedures on patients with suspected or confirmed infectious TB disease inside a patient's home. Sputum collection should be performed outdoors, away from other persons, windows, or ventilation intakes.

Health care workers who visit TB patients at their homes should take these precautions to protect themselves from exposure to M tuberculosis:

• Instruct patients to cover their mouth and nose with a tissue when coughing or sneezing;
• Wear a personal respirator when visiting the home of an infectious patient with TB or when transporting an infectious patient with TB in a vehicle;
• When it is necessary to collect a sputum specimen in the home, collect the specimen in a well-ventilated area, away from other household members; if possible, the specimen should be collected outdoors; and
• Participate in a TB testing and prevention program.

Patients should also be instructed about the signs and symptoms of adverse effects of the medications used to treat TB, particularly those that may indicate drug-induced hepatitis, ocular damage, or peripheral neuropathy.

NH: Abdominal pain, dark urine, fatigue, fever for more than three days, flu-like symptoms, nausea, vomiting, and yellow coloring of the eyes or skin (Drug-induced hepatitis). Numbness or tingling in the face or extremities (Peripheral neuropathy).

• Ethambutol: blurred vision, any change in vision or color perception.
• Pyrazinamide: Anorexia, fatigue, joint pain, nausea, vomiting.
• Rifampin: Abdominal pain, dark urine, fatigue, fever for more than three days, flu-like symptoms, nausea, vomiting, and yellow coloring of the eyes or skin (Drug-induced hepatitis).

Patients should also be instructed on the importance of adhering to the medication regimen and the consequences of non-compliance.

The only TB vaccine currently available is Bacillus Calmette-Guérin (BCG). Bacillus Calmette-Guérin vaccine is not routinely used in the US, but many foreign-born persons have been BCG-vaccinated. BCG is primarily used in countries with a high prevalence of TB to prevent childhood tuberculous meningitis and miliary disease. Vaccination with BCG may be done in either of these circumstances (Von Reyn, 2019).

Children: Children with a negative tuberculin skin test who are in a living situation in which the likelihood of exposure to TB is high and the child cannot be removed from that situation. Vaccination should also be done if the child is continually exposed to TB and cannot be treated or has TB resistant to INH and Rifampin. The vaccine is 70%-80% effective (Von Reyn, 2019).

Healthcare workers: Healthcare workers who are exposed to a high percentage of patients with M tuberculosis resistant to INH and Rifampin should be vaccinated with BCG. Healthcare workers should be vaccinated with BCG if there is ongoing transmission of drug-resistant M tuberculosis strains to healthcare workers and subsequent infection is likely, or comprehensive TB infection-control precautions have been implemented but have not been successful.

The BCG vaccine is much less effective for older children and adults, likely due to differences in immune status between infants and these groups and because older children and adults are more likely to have had prior exposure to TB (Von Reyn, 2019).

BCG vaccination should not be given to people who are immunosuppressed (e.g., HIV infected) or who are likely to become immunocompromised (e.g., persons who are candidates for organ transplant) as these patients may develop serious systemic adverse effects.

BCG vaccination should not be given during pregnancy. Even though no harmful effects of BCG vaccination on the fetus have been observed, BCG is a live vaccine, so its use in pregnant women is contraindicated.

BCG is relatively safe. Large local reactions at the injection site are common, and they may become ulcerated and painful and leave a permanent (Von Reyn, 2019). Osteitis and osteomyelitis can occur after a BCG injection, but these are rare adverse effects. Disseminated BCG infections in the liver, lymphatic issue, skeletal system, the CNS, and other sites can also occur, most often in patients who are immunocompromised and disseminated BCG disease has been reported to occur in 33% of immunocompromised infants (Von Reyn, 2019).

Vaccination with BCG can cause a false-positive TB skin test (CDC, 2016c). The BCG vaccine does not affect the IRGA test (Von Reyn, 2019).

Disseminated TB, sometimes referred to as military TB, is defined as TB caused by hematogenous dissemination of M tuberculosis and is present in two or more non-contiguous sites (Khan, 2019). Disseminated TB is an uncommon condition. It accounts for 2%-3% of all cases of TB, and disseminated TB can affect organs and tissues, including (but not limited to) the bone marrow, eyes, kidneys, and liver (Khan, 2019). Disseminated TB may be caused by reactivation of latent TB, the progression of active TB, or it may be iatrogenic. Disseminated TB occurs most often in patients with specific risk factors, and people who are immunocompromised or have an HIV infection are particularly susceptible (Khan, 2019).

Tuberculosis is a serious disease for children. Children are more susceptible to the transmission of TB, and they should be screened if they have had close contact with someone who has the disease or if they have risk factors, e.g., an HIV infection, that increases their risk of becoming infected. For children, brief contact with an infected adult may result in infection, the risk of progression to the active disease after exposure to TB is quite high, up to 50% in children < two years of age and children are more likely than adults to develop severe or extrapulmonary TB (Carvalho et al., 2018). Worldwide, Tuberculosis is a commonly occurring disease, but in the United States, pediatric cases of TB are rare; in 2016, there were only 387 reported cases of TB in children and adolescents under the age of 15 (CDC, 2016).

Active TB in children is treated with two-month initiation and four-month continuation phases. The recommended dosing for INH differs slightly depending on the source (The recommendation from the WHO is 7-15 mg/kg, the other sources are 10-20 mg), and the dosing of the TB drugs can be done once, twice, or three times a week dosing; the decision to which to use depends on the incidence of TB in the area, the HIV status of the child, and other factors. The regimen is listed below (WHO, 2014):

Initiation

INH: Daily dosing, 10-15 mg/kg. Twice a week dosing, 20-30 mg/kg. The 24-hour maximum dose is 300 mg.

Rifampin: Once a day or twice weekly dosing, 15-20 mg/kg, 600 mg maximum daily dose.

Pyrazinamide: Daily dosing, 30-40 mg/kg. Twice a week dosing, 50 mg/kg. For both. The 24-hour maximum dose is 2 grams.

Ethambutol: 15-25 mg/kg, the 24-hour maximum dose is 1 gram. Twice a week dosing, 50 mg/kg with a 24-hour maximum dose of 2.5 grams.

Continuation

INH: Daily dosing, 10-15 mg/kg. Twice a week dosing, 20-30 mg/kg. The 24-hour maximum dose is 300 mg.

Rifampin: Once a day or twice weekly dosing, 15-20 mg/kg, 600 mg maximum daily dose.

Children with suspected or confirmed pulmonary Tuberculosis or tuberculous peripheral lymphadenitis who live in settings with low HIV prevalence or low resistance to isoniazid and children who are HIV-negative can be treated with a three-drug regimen (INH, rifampicin, and pyrazinamide) for 2 months followed by a two-drug (INH and rifampicin) regimen for 4 months using the aforementioned doses/dosing schedule (WHO, 2014).

Children with suspected or confirmed pulmonary TB or tuberculosis peripheral lymphadenitis or children who have extensive pulmonary disease, living in settings where the prevalence of HIV is high or where INH resistance is high should be treated with the aforementioned four-drug/two months, two-drug/four months regimen (WHO, 2014).

Infants aged 0–3 months with suspected or confirmed pulmonary Tuberculosis or tuberculous peripheral lymphadenitis should be treated with previously outlined regimens. Dose adjustments may be needed, and these should be determined by a clinician who is experienced in managing pediatric Tuberculosis (WHO, 2014).

Children with suspected or confirmed pulmonary tuberculosis or tuberculosis peripheral lymphadenitis living in settings with a high HIV prevalence or who have a confirmed HIV infection should not be treated with intermittent regimens, twice-weekly or thrice-weekly regimens. If the child does not have an HIV infection and DOT can be done, a thrice-weekly regimen can be used (WHO, 2014).

Streptomycin should not be used as part of first-line treatment regimens for children with pulmonary Tuberculosis or tuberculous peripheral lymphadenitis.

Children treated for drug-susceptible TB do not need to take pyridoxine (Adams & Starke, 2019).

Treatment of children with MDR-TB is essentially the same as it is for adults, but there are several considerations to consider when treating children for MDR-TB (WHO, 2019).

The short or long duration of treatment can be used, but there is less clinical experience with the shorter duration (WHO, 2019). Bedaquiline can be used in children under six and delamanid at three years of age (WHO, 2019). Amikacin and streptomycin are ototoxic and nephrotoxic, and they should be given to children who have MDR-TB only if there is no other option, monitoring for otic and renal adverse effects cannot be done, and the TB strain the child has is susceptible to these drugs (WHO, 2019).

Treatment of children who have or are suspected of having latent TB is not significantly different from the treatment for adults. If the diagnosis of latent TB is made, four treatment regimens can be used (Carvalho et al., 2018). There is no evidence that any regimen is superior to another, so the clinician should use the approach that is likely to promote adherence and is the least toxic to the child. Daily pyridoxine supplementation for children taking INH is unnecessary unless the child is exclusively breastfed, has an HIV infection and is symptomatic, he/she has a milk/meat deficient diet, or if the child had a nutritionally deficient diet (Adams & Starke, 2018).

INH: Once a day at 10 to 15 mg/kg. The duration of therapy is nine months, and the daily dose should not exceed 300 mg. INH can also be given at a dose of 20 to 30 mg/kg, twice a week for nine months, with the daily dose not to exceed 900 mg. The latter approach requires DOT.

INH and Rifampin: INH is given at 10 to 15 mg/kg a day, and the daily dose should not exceed 300 mg. Rifampin is dosed at 10 to 20 mg/kg daily, and the daily dose should not exceed 600 mg. The duration of therapy is three months.

INH and rifapentine: INH is given once a week for three months at 15 mg/g. The dose should be rounded up to the nearest 50 or 100 mg, and the daily dose should not exceed 900 mg. The rifapentine dose depends on the patient's weight and is given once a week for three months. DOT is preferred for this approach.

• 10-14 kg: 300 mg
• 14.1-25 kg: 450 mg
• 25.1-32 kg: 600 mg
• 32.1-49.9 kg: 750 mg
• ≥ 50 kg: 900 mg, maximum

Rifampin: 10 to 20 mg/kg a day for four months. The daily dose should not exceed 600 mg.

A 45-year-old female who recently emigrated to the United States from Southeast Asia 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 the presence of Tuberculosis, 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 diagnoses the patient as having a stress headache and that the cough may be likely 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 may be difficult. She recommends that the patient be tested for hepatitis B and C, HIV, pregnancy, and TB; a TST or IRGA can be used, but the IRGA is preferable if it is likely that the patient may not return for a TST reading within the prescribed time. In addition, CXR and liver function tests are done, and the patient's visual acuity is checked.

The IRGA is positive. The CXR and liver function tests are normal, as is her visual acuity, the patient does not have hepatitis B or C or HIV, and she is not pregnant. The infectious disease specialist has consulted again, and because of the patient's place of origin and possibly close contact with someone who may have had active TB, she is at risk for progression of her (likely) latent TB to the active disease. Rifampin, 10 mg/kg taken once a day for four months, is prescribed. The patient is evaluated monthly at the clinic, and at the end of the drug therapy, there is no clinical evidence that she has active TB.

A 19-year-old male self-refers to an emergency room complaining of cough, fever, and night sweats, duration of approximately two weeks. The patient has PMH of alcohol abuse and IV drug use, a chronic hepatitis C infection (untreated), is taking ART for his HIV infection and is currently homeless. The patient is admitted to the hospital, placed in a private room, and standard and respiratory 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 WBC and mildly elevated ALT, 99 IU/L (it is not known if the patient's baseline ALT is elevated), and his TST result is > 5 mm (Note: He has not been previously had a TST. He does not have hepatitis B.

Because there is a high suspicion that the patient has active TB, an empiric regimen of INH, ethambutol, Rifampin, and pyrazinamide is suggested as well as a daily supplement of pyridoxine. Because the patient is on ART, a clinical pharmacologist is consulted before beginning the TB drug therapy to determine what adjustments should be made in the TB drug therapy and the ART and if Rifampin can be used. A sputum culture confirms the presence of TB, drug susceptibility determines that the patient does not have MDR-TB or XDR-TB, and drug therapy is started. It is decided to delay treatment of his hepatitis C for the time. 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.

Tuberculosis is increasingly uncommon in the United States. However, recent immigrants, people infected with HIV, the elderly, and people with certain risk factors are susceptible to developing primary disease or reactivation of latent TB. Some of these populations (e.g., the elderly and people with medical risk factors) are increasing yearly. Elimination of TB depends on targeted screening for latent TB, strict adherence to drug regimens, and the proper use of infection control techniques for hospitalized patients with TB. TB could be effectively eliminated if screening, treatment, and infection control are done properly.

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