Resistance to EMB is less common than that to the other first-line drugs. Mycobacterium tuberculosis. Active disease is much more likely in patients with impaired immunity, particularly those with HIV infection. Ethambutol (EMB) is given orally and is the best-tolerated of the first-line drugs. However, the effect of BCG vaccination on TST wanes after several years; after this time, a positive test is likely to be due to TB infection. From developing new therapies that treat and prevent disease to helping people in need, we are committed to improving health and well-being around the world. Tobacco use also is a risk factor. lthough extrapulmonary tuberculosis (TB) had been observed for many centuries, the exact incidence of disseminated TB is still unclear. Therefore, ITB can often mimic CD in clinical features and gross pathology. It accelerates metabolism of anticoagulants, oral contraceptives, corticosteroids, digitoxin, oral antihyperglycemic drugs, methadone, and many other drugs. Most patients with TB can be treated as outpatients, with instructions on how to prevent transmission usually including, Avoiding visitors (except for previously exposed family members), Covering coughs with a tissue or an elbow. Symptoms of CD include moderate to severe abdominal pain, bloody stool, and weight loss. Kanamycin and amikacin may remain effective even if streptomycin resistance has developed. You are more likely to get this type of TB if you have a weakened immune system due to disease (such as AIDS) or certain medicines. If an Xpert MTB/RIF test on a sputum sample is positive, the diagnosis of pulmonary TB is considered confirmed. DOT increases the likelihood that the full treatment course will be completed from 61% to 86% (91% with enhanced DOT, in which incentives and enablers such as transportation vouchers, child care, outreach workers, and meals are provided). Links to other sites are provided for information only -- they do not constitute endorsements of those other sites. Tuberculous arthritis usually affects the hips and knees. Adverse effects of streptomycin include rash, fever, agranulocytosis, and serum sickness. The resulting lung infection is called primary TB. New cases declined 1.5% between 2014 and 2015, extending a trend that has been occurring for a number of years. A well-demarcated bleb or wheal should result immediately. Flushing and tingling around the mouth commonly accompany injection but subside quickly. The tissue that is affected, such as the bones or joints, may have permanent damage due to the infection. Disseminated tuberculosis is a mycobacterial infection in which mycobacteria have spread from the lungs to other parts of the body through the blood or lymph system. Culture is also required to isolate bacteria for drug-susceptibility testing and genotyping. Clinicians should also check for other common causes (eg, nonadherence, extensive cavitary disease, drug resistance, malabsorption of drugs). The increasing popularity of cheese made from unpasteurized milk raises new concerns if the cheeses come from countries with a bovine TB problem (eg, Mexico, the United Kingdom). Symptoms Disseminated tuberculosis can affect many different body areas. Case rates vary widely by country, age, race, sex, and socioeconomic status. Symptoms include productive cough, fever, weight loss, and malaise. Some fluoroquinolones (levofloxacin, moxifloxacin) are the most active and safest TB drugs after isoniazid and rifampin, but they are not first-line drugs for TB susceptible to isoniazid and rifampin. It is critical to give the injection intradermally, not subcutaneously. Infants and older adults are also at higher risk. If patients cannot produce sputum spontaneously, aerosolized hypertonic saline can be used to induce it. Management of drug-resistant TB varies with the pattern of drug resistance. These tests should be repeated if patients continue to produce culture-positive sputum after 3 mo of treatment or if cultures become positive after a period of negative cultures. Most patients with uncomplicated tuberculosis and all patients with complicating illnesses (eg, AIDS, hepatitis, diabetes), adverse drug reactions, or drug resistance should be referred to a TB specialist. Your health care team will ensure that you receive the best care. Chest pain (can also result from tuberculous acute pericarditis) 7. TB of the tonsils, lymph nodes, abdominal organs, bones, and joints was once commonly caused by ingestion of milk or milk products (eg, cheese) contaminated with M. bovis, but this transmission route has been largely eradicated in developed countries by slaughter of cows that test positive on a tuberculin skin test and by pasteurization of milk. The Merck Manual was first published in 1899 as a service to the community. Hematogenous dissemination is less likely in patients with partial immunity due to vaccination or to prior natural infection with M. tuberculosis or environmental mycobacteria. However, daily therapy is recommended for patients with MDR-TB or HIV coinfection. Fatigue 5. 9th ed. Dry cough 6. Incomplete, erratic, or single-drug therapy selects for these resistant organisms. Infection with MAC is not contagious and, in HIV-infected patients, affects primarily the blood and bone marrow, not the lungs. Infants, young children, and immunocompromised children (e.g., children with HIV) are at the highest risk of developing the most severe forms of TB such as TB meningitis or disseminated TB disease. In the early weeks of infection, some infected macrophages migrate to regional lymph nodes (eg, hilar, mediastinal), where they access the bloodstream. Fitzgerald DW, Sterling TR, Haas DW. It is best visualized in an apical-lordotic view or with chest CT. Middle and lower lung infiltrates are nonspecific but should prompt suspicion of primary TB in patients (usually young) whose symptoms or exposure history suggests recent infection, particularly if there is pleural effusion. The mildest form produces no signs or symptoms, but severe infections can be life-threatening. Because risk of exposing other hospitalized patients is high, even though patients receiving effective treatment become noncontagious before sputum smears become negative, release from respiratory isolation usually requires 3 negative sputum smears over 2 days, including at least one early-morning negative specimen. Treatment is with multiple antimicrobial drugs given for at least 6 mo. Close contacts of an active case and others at high risk and with a negative TST or IGRA should also be considered for preventive treatment unless contraindicated. *Specific regimens are discussed in text. A person who is infected with a drug-resistant strain from another person is said to have primary drug resistance. Disseminated disease can occur within weeks of the primary infection. The interactions of rifamycins and many antiretroviral drugs are particularly complex; combined use requires specialized expertise. Thus, patients coinfected with HIV and not receiving appropriate ART have about a 10% annual risk of developing active disease. How contagious patients with untreated active pulmonary TB are varies widely. Their renal and neural toxicities are similar to those of streptomycin. Now, outcomes are somewhat better in developed countries because of earlier TB diagnosis and antiretroviral therapy, but TB in HIV patients remains a serious concern. Thus, it is considered worthwhile in high-burden regions. In: Bennett JE, Dolin R, Blaser MJ, eds. The classic symptoms of active TB are a chronic cough with blood-containing mucus, fever, night sweats, and weight loss. However, with effective antiretroviral therapy (and appropriate anti-TB treatment), the prognosis for patients with HIV infection, even those with MDR-TB, may approach that of immunocompetent patients. Chills 3. The effectiveness of this vaccine is limited and it is not routinely used in the United States. Skin rashesLess common symptoms that may be related to disseminated tuberculosis include: 1. Results can be falsely negative, most often in patients who are febrile, elderly, HIV-infected (especially if CD4 count is < 200 cells/μL), or very ill, many of whom show no reaction to any skin test (anergy). verify here. Other antibiotics are active against TB and are used primarily when patients have drug-resistant TB (DR-TB) or do not tolerate one of the first-line drugs. Of those infected, perhaps 15 million have active disease at any given time. Pyrazinamide (PZA) is an oral bactericidal drug. Treatment of all patients with new, previously untreated TB should consist of a. Ghon foci and affected hilar lymph nodes are much less likely to be sites of reactivation. Mechanical drug monitoring devices have been advocated to improve adherence with SAT. Culture can detect as few as 10 bacilli/mL of sputum and can be done using solid or liquid media. People who have been exposed to TB should be skin tested immediately and have a follow-up test at a later date, if the first test is negative. It can also cause a violent reaction to disulfiram, a drug occasionally used for alcoholism. A variable percentage of latent infections subsequently reactivate with symptoms and signs of disease. Recommended cutoff points for a positive reaction depend on the clinical setting: 5 mm: Patients at high risk of developing active TB if infected, such as those who have chest x-ray evidence of past TB, who are immunosuppressed because of HIV infection or drugs (eg, TNF-alpha inhibitors, corticosteroid use equivalent to prednisone 15 mg/day for > 1 mo), or who are close contacts of patients with infectious TB, 10 mm: Patients with some risk factors, such as injection drug users, recent immigrants from high-prevalence areas, residents of high-risk settings (eg, prisons, homeless shelters), patients with certain disorders (eg, silicosis, renal insufficiency, diabetes, head or neck cancer), and those who have had gastrectomy or jejunoileal bypass surgery, 15 mm: Patients with no risk factors (who typically should not be tested). Call 911 for all medical emergencies. Latent infection occurs after most primary infections. Moxifloxacin appears to be as active as isoniazid when used with rifampin. M. tuberculosis bacilli initially cause a primary infection, which uncommonly causes acute illness. Although BCG vaccination often converts the TST, the reaction is usually smaller than the response to natural TB infection, and it usually wanes more quickly. Tuberculosis (TB) is a chronic, progressive mycobacterial infection, often with a period of latency following initial infection. Sites of latent infection are dynamic processes, not entirely dormant as once believed. For patients with proven drug-susceptible or MDR-TB, precautions are maintained until there is a clinical response to therapy (typically, 1 to 2 wk). Because induction of sputum and bronchoscopy entail some risk of infection for medical staff, these procedures should be done as a last resort in selected cases. Smear-negative TB is more common when HIV coinfection is present. The prevalence of disseminated tuberculosis was 1.7 %. Still, TB causes or contributes to death in about 10% of cases, often in patients who are debilitated for other reasons. Drug resistance is a major concern and is increased by poor adherence, use of inappropriate drug regimens, and inadequate susceptibility testing. Pre-XDR-TB is MDR-TB plus resistance to either a fluoroquinolone or an injectable drug but not both. INH causes asymptomatic, transient aminotransferase elevations in up to 20% of patients and clinical (usually reversible) hepatitis in about 1/1000. Tuberculomas (mass lesions in the lungs or CNS due to TB) are more common and more destructive. Joint pain 6. It is also used in a 12-dose, once/wk DOT regimen with INH for TB prophylaxis. The frequent presence of other disorders in old age further complicates the diagnosis. Disseminated TB develops in the small number of infected people whose immune systems do not successfully contain the primary infection. In some patients, active disease develops when they are reinfected rather than when latent disease reactivates. Symptoms of TB disease in other parts of the body depend on the area affected. Diagnosis is most often by sputum smear and culture and, increasingly, by rapid molecular-based diagnostic tests. CDC: Tuberculosis—United States, 2016. TB damages tissues through delayed-type hypersensitivity (DTH), typically producing granulomatous necrosis with a caseous histologic appearance. Resistant strains can be transmitted from person to person. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases. In the prechemotherapy era, TB empyema sometimes complicated medically induced pneumothorax therapy and was usually rapidly fatal, as was sudden massive hemoptysis due to erosion of a pulmonary artery by an enlarging cavity. Surgical face masks for TB patients are stigmatizing and are typically not recommended for cooperative patients. Infection of other organs can cause a wide range of symptoms. Streptomycin is contraindicated during pregnancy because it may cause vestibular toxicity and ototoxicity in the fetus. INH delays hepatic metabolism of phenytoin, requiring dose reduction. However, sensitivity is lower than that of Xpert MTB/RIF. Drug resistance develops through spontaneous genetic mutation. Only about 50% of patients complete the recommended 9-mo course of INH. Symptoms include productive cough, fever, weight loss, and malaise. In this case, medicines may be given 2 or 3 times a week, as prescribed by a provider. When there is concern that a person may not take all the medicines as directed, a provider may need to watch the person take the prescribed medicines. The first-line drugs isoniazid (INH), rifampin (RIF), pyrazinamide (PZA), and ethambutol (EMB) are used together in initial treatment (for regimens and doses, see Tuberculosis (TB) : Treatment regimens and Dosing of Oral First-Line Anti-TB Drugs*). Over half of these cases occurred in patients born outside the US in high-prevalence areas. Hemoptysis occurs only with cavitary TB (due to granulomatous damage to vessels but sometimes due to fungal growth in a cavity). Approximately 70% of all cervical cancers are caused by which of the following types of human papilloma virus (HPV)? In patients with untreated HIV infection and LTBI, active TB develops in about 5 to 10%/yr, whereas in people who are not immunocompromised, it develops in about the same percentage over a lifetime. Infection of the bone marrow may cause severe anemia and other blood abnormalities, suggesting leukemia. TB lymphadenopathy is the most common extrapulmonary presentation; however, meningitis is the most feared because of its high mortality in the very young and very old. Sometimes, it does not occur until years after you become infected. Symptoms depend on the affected areas of the body and can include: The health care provider will perform a physical exam. Cavitary disease is less common than in adults, and most children harbor far fewer organisms and are not contagious. In the US, most children and other people without specific TB risk factors should not be tested to avoid false-positive reactions. The new anti-TB drugs bedaquiline, delamanid, and sutezolid are active against resistant strains and may help control the epidemic of drug-resistant TB. TB most commonly affects the lungs. Importantly, they are often negative in patients with remote TB infection. This approach is called directly observed therapy. For patients who are highly contagious as evidenced by multiple family members with disease or positive skin tests, even relatively casual contacts (eg, passengers on the bus they ride) should be referred for skin testing and evaluation for latent infection; patients who do not infect any household contacts are less likely to infect casual contacts. Perhaps only a single organism may suffice to cause infection in susceptible people, but less susceptible people may require repeated exposure to develop infection. If this dose is tolerated (typically in about half of patients), the full dose may be restarted with close monitoring for recurrence of symptoms and deterioration of liver function. 2. WHO: Tuberculosis Fact Sheet, 2017. It remains the single most useful and least expensive drug for TB treatment. This situation results in ongoing transmission, low cure rates, and amplified resistance. When used during the intensive initial 2 mo of treatment, it shortens the duration of therapy to 6 mo and prevents development of resistance to RIF. The following symptoms of disseminated pulmonary tuberculosis appear first: weakness, increased sweating, worsening of appetite, fever, headache, and sometimes dyspepsia. Regardless of their age, nursing home residents who were previously TST negative are at risk of disease due to recent transmission, which may cause apical, middle-lobe, or lower-lobe pneumonia as well as pleural effusion. Abdominal pain or swelling 2. Patients with optic neuritis present initially with an inability to distinguish blue from green, followed by impairment of visual acuity. Fever 2. Transmission is enhanced by frequent or prolonged exposure to untreated patients who are dispersing large numbers of tubercle bacilli in overcrowded, poorly ventilated enclosed spaces; consequently, people living in poverty or in institutions are at particular risk. Infectious foci may leave fibronodular scars in the apices of one or both lungs (Simon foci, which usually result from hematogenous seeding from another site of infection) or small areas of consolidation (Ghon foci). INH or PZA, rather than RIF, is the more likely cause of hepatotoxicity. 3. Fatigue 8. This test is usually done only on smear-positive specimens. The BCG vaccine, made from an attenuated strain of M. bovis is given to > 80% of the world’s children, primarily in high-burden countries. Disseminated TB usually develops insidiously with systemic symptoms such as fever, weakness, weight loss, fatigue, and anorexia. Lung lesions are characteristically but not invariably cavitary, especially in immunosuppressed patients with impaired DTH. Then it may be given twice/wk for another 2 mo if necessary. Anyone entering the room should wear a respirator (not a surgical mask) that has been appropriately fitted and that meets National Institute for Occupational Safety and Health certification (N-95 or greater). MDR-TB is resistant to isoniazid and rifampin, with or without resistance to other drugs. Weight loss Fever 6. Drenching night sweats are a classic symptom but are neither common in nor specific for TB. Treatment of XDR-TB has even less favorable outcomes; the mortality rate is extremely high in patients coinfected with HIV, even when they are being treated with antiretroviral drugs. In the early 1990s, half of HIV-infected TB patients who were untreated or infected with an MDR strain died, with median survival of only 60 days. If NAAT and AFB smear results are negative or if AFB smear results are positive and NAAT results are negative, clinical judgment is used to determine whether to begin anti-TB treatment while awaiting results of culture. The tuberculin skin test and interferon-gamma release blood assays (IGRA) become positive during the latent stage of infection. Infection usually begins from a single droplet nucleus, which typically carries few organisms. Small pleural effusions are predominantly lymphocytic, typically contain few organisms, and clear within a few weeks. All medicines are continued until lab tests show which work best. Symptoms depend upon the organ system infected with the bacteria. All forms of TB and exposure need prompt evaluation and treatment. CSF penetration is poor, and intrathecal administration should not be used if other effective drugs are available. Low-grade fever is common but not invariable. A Ghon focus with lymph node involvement is a Ghon complex, which, if calcified, is called a Ranke complex. In active pulmonary tuberculosis, even moderate or severe disease, patients may have no symptoms, except “not feeling well,” along with anorexia, fatigue, and weight loss, which develop gradually over several weeks, or they may have more specific symptoms. Patients being treated for LTBI should be instructed to stop the drug if they experience any new symptoms, especially unexplained fatigue, loss of appetite, or nausea. The TB bacteria can become resistant to treatment. For both initial and continuation phases, the total number of doses (calculated by doses/wk times number of weeks) should be given; thus if any doses are missed, treatment is extended and not stopped at the end of the time period. PZA is commonly used during pregnancy, but its safety has not been confirmed. 3. These drugs can be given daily throughout this phase or daily for 2 wk, followed by doses 2 or 3 times/week for 6 wk. Lymphadenitis (scrofula) is the most common extrapulmonary manifestation, but TB may also affect the vertebrae (Pott disease), the highly vascular epiphyses of long bones, or the CNS and meninges. Public health departments usually visit homes to do the following: Evaluate potential barriers to treatment (eg, extreme poverty, unstable housing, child care problems, alcoholism, mental illness). Presumed activity is based on drug susceptibility test results, a known source case, prior exposure to anti-TB drugs, or drug susceptibility patterns in the community. In this way, the organism can become resistant to multiple antibiotics in steps. Cough 2. Risk of being infected is increased for people who live in group facilities, such as shelters, long-term care facilities, or correctional facilities, and for those who have been homeless in the past year. When used with clarithromycin or fluconazole, rifabutin has been associated with uveitis. The CDC recommends that all TST reactions in children who have had BCG be attributed to TB infection (and treated accordingly) because untreated latent infection can have serious complications. Cough and dyspnea also may be prominent symptoms. Patients who require immunosuppression after solid organ transplantation are at the highest risk, but other immunosuppressants such as corticosteroids and TNF inhibitors also commonly cause reactivation. In some studies, IGRAs appear to perform better than the TST in immunocompromised patients, although this advantage has not yet been established. HIV infection reduces both inflammatory reaction and cavitation of pulmonary lesions.

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