Tuberculosis overview

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Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Tuberculosis from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Children

HIV Coinfection

Diagnosis

History and Symptoms

Physical Examination

Laboratory Findings

Electrocardiogram

Chest X Ray

CT

MRI

Echocardiography or Ultrasound

Other Imaging Findings

Other Diagnostic Studies

Treatment

Medical Therapy

Special Conditions
Drug-resistant

Surgery

Primary Prevention

Secondary Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Alejandro Lemor, M.D. [2]; João André Alves Silva, M.D. [3]; Ammu Susheela, M.D. [4]

Overview

Tuberculosis (abbreviated as TB or Tuberculosis) is a common infectious disease caused by Mycobacterium tuberculosis. Tuberculosis most commonly involves the lungs as the organism thrives in high oxygen environments, but it can also cause disease in the central nervous system, the lymphatic system, the circulatory system, the genitourinary system, bones, joints and even the skin. Over one-third of the world's population has been exposed to M. tuberculosis, and new infections occur at a rate of one per second. Not all individuals exposed to the bacterium develop clinically overt tuberculosis infection; in fact, asymptomatic, latent TB infection discovered by screening is more common. Approximately, one in ten latent infections progresses to active (symptomatic) TB disease, which, if left untreated, carries mortality rates of up to 50%. Symptoms include shortness of breath, hemoptysis, fever, chills, night sweats, and weight loss. Several treatment regimens are available for the latent and active forms of TB. Classically, a prolonged course of 6-9 months of a single agent (rifampin or isoniazid) is administered to patients with latent TB, while a more aggressive course that consists of 4 major anti-tuberculous agents (rifampin, isoniazid, ethambutol, pyrazinamide) is reserved for patients with active disease.

Historical Perspective

Classification

TB Classification System

  • According to the CDC, the clinical classification system for TB used in the United States is based on the pathogenesis of the disease.
  • This classification system provides clinicians the opportunity to keep an eye on the development of TB in their patients.
  • Health care providers should follow with state and local laws and regulations requiring the reporting of TB disease.
  • All persons with Class 3 or Class 5 TB should be reported directly to the local or state health department.
  • A patient should not have a Class 5 classification for more than 3 months.
Class Type Description
0 No TB exposure
Not infected
No history of TB exposure and no evidence of M. tuberculosis infection or disease
Negative reaction to TST or IGRA
1 TB exposure
No evidence of infection
History of exposure to M. tuberculosis
Negative reaction to TST or IGRA (given at least 8 to 10 weeks after exposure)
2 TB infection
No TB disease
Positive reaction to TST or IGRA
Negative bacteriological studies (smear and cultures)
No bacteriological or radiographic evidence of active TB disease
3 TB clinically active Positive culture for M. tuberculosis OR
Positive reaction to TST or IGRA, plus clinical, bacteriological, or radiographic evidence of current active TB
4 Previous TB disease (not clinically active) May have past medical history of TB disease
Abnormal but stable radiographic findings
Positive reaction to the TST or IGRA
Negative bacteriologic studies (smear and cultures)
No clinical or radiographic evidence of current active TB disease
5 TB suspected Signs and symptoms of active TB disease, but medical evaluation not complete

Pathophysiology

Tuberculosis is a granulomatous infection that is chiefly transmitted through droplets. The granuloma encloses mycobacteria and prevents their spreading and facilitates immune immune cell communication. Within the granuloma, T lymphocytes (CD4) releases cytokines, such as interferon gamma, that activates local macrophages. It is asymptomatic in 90% of immunocompetent individuals. In symptomatic patients, it can present as pulmonary or extrapulmonary manifestations. The primary infection may turn into disseminated infection. Tuberculosis usually has an impact the progression of HIV if present together. Depending on the age of the patient, tuberculosis may have different clinical manifestations, progression, and prognosis.

Causes

Mycobacterium tuberculosis is the bacterium responsible for tuberculosis. It is an aerobic, non-encapsulated, non-motile, acid-fast bacillus. M. tuberculosis is one of the Mycobacterium tuberculosis complex, which also includes bacteria, such as M. bovis and M. africanum. The bacterium has a very slow rate of replication, and its genetic variations account for the geographical distribution of different strains, and are involved in drug resistance. M. tuberculosis has tropism for different kinds of human cells, with preference for cells of the lung. It may infect different species, but human beings are its frequent natural reservoir.

Epidemiology and Demographics

In 2015, about 10.4 million people developed symptomatic TB and 1.8 million died from the disease. there were 9,421 reported cases in the United States in 2014 with an incidence of 3.0 per 100,000 persons. Since 1990, the mortality rate was steadily decreasing. The prevalence of TB increases with age and it is higher in older men. TB is more prevalent in racial and ethnic minorities than non-Hispanic whites. TB is an major cause of death in people coinfected with HIV. A third of deaths among these patients is due to TB. In 2015, 60% of TB cases worldwide occurred in 6 countries: South Africa, Indonesia, Nigeria, Pakistan, India, and China. The WHO has identified 24 other high-burden TB countries including Bangladesh, Congo, Columbia, Lesotho, Cambodia, Korea, Brazil, Ethiopia, Myanmar, Mozambique, Thailand, Angola, Zambia, Vietnam, Kenya, Central Africa, Russia, Liberia, Tanzania, Zimbabwe, Namibia, Philippines, Sierra Leone, Papua New Guinea.

Risk Factors

The risk factors for the development of tuberculosis include: weakened immune system (patients taking immunosuppressive medication or with immunosuppressive diseases, such as HIV or diabetes); history of contact with infected patients, bad hygiene conditions, and evidence of previous tuberculosis. Risk factors for multidrug-resistant TB include: non-adherence to the treatment regimen, insufficient medication for that strain of bacteria, and contact with patients with multidrug-resistant TB.

Screening

Screening for tuberculosis is generally done by using a mantoux tuberculin skin test, also known as a tuberculin skin test or a PPD. The test involves injecting a small amount of a purified protein derivative of the tuberculosis bacterium intradermally and watching for a reaction in the following days.

Natural history, complications and prognosis

Tuberculosis has been classified as a primary or secondary (post-primary) infection. It can have pulmonary and extra pulmonary manifestations as well as severe parenchymal, vascular, pleural, and chest wall complications. Pulmonary complications include pleural effusions, cavitations, lymphadenopathy, airway obstruction, pneumonia and bronchiectasis. The hematogenous dissemination of infection can lead to miliary tuberculosis. The post-primary infection can be due to a recent infection or reactivation of an old infection. Without treatment, 1/3 of patients with active tuberculosis dies within 1 year of the diagnosis, and more than 50% during the first 5 years. But with early diagnosis and treatment, it has a good prognosis.

Diagnosis

History and Symptoms

The general symptoms of tuberculosis include weakness, weight loss, fever, and night sweats. Symptoms of pulmonary tuberculosis include cough, chest pain, and hemoptysis. Tuberculosis is particularly difficult to diagnose in children, as these may not present with common findings.

Physical Examination

A physical examination can give an overview about the general condition and other factors that may influence the tuberculosis response to treatment, such as HIV infection or other diseases. The most common physical findings include fever, decreased breath sounds, tachypnea and tachycardia. Physical findings will depend on the location of the tuberculosis infection.

Laboratory findings

Routine laboratory exams are usually in the normal ranges. The presence of acid-fast-bacilli (AFB) on a sputum smear or another specimen often indicates TB disease and a positive culture for M. tuberculosis confirms the diagnosis. Other laboratory tests include peritoneal fluid or CSF analysis, urinalysis, and Interferon-Gamma release assays.

Electrocardiogram

Echocardiography or Ultrasound can be helpful in patients who develop pericardial effusion secondary to TB. In rare occasions TB may lead to congestive heart failure, in which case echocardiograph may also help in the diagnosis. Common findings in CHF on the echocardiogram include: hypokinesia; valvular insufficiency; and enlargement of all heart chambers.

Chest X-Ray

A chest X-ray is one of the important diagnostic tools in tuberculosis. A chest radiograph may be used to rule out the possibility of pulmonary TB in a person who are symptomatic or had a positive reaction to a tuberculin test or QFT-G and no symptoms of the disease. The findings on chest x-ray can be divided into parenchymal and pleural. The early parenchymal findings can be infiltrated, and cavity. A healed tuberculotic lesion can present as fibrosis, and calcification. Pleural lesions in form of pleural effusion can also be seen. An advanced tuberculosis lesion can present a combination of these early lesions and termed fibrocavitary lesions.

CT

The majority of patients with pulmonary tuberculosis will have abnormal findings in a chest CT, which include micronodules, interlobular septal thickening, cavitation and consolidation. CT scan is more sensitive than an X-ray to detect lymphadenopathies.

MRI

MRI is used for the assessment of extrapulmonary tuberculosis, such as CNS tuberculosis, Pott's disease, and parotid gland tuberculosis.

Echocardiography or Ultrasound

Echocardiography or Ultrasound can be helpful in patients who develop pericardial effusion secondary to TB. In rare occasions TB may lead to congestive heart failure, in which case echocardiograph may also help in the diagnosis. Common findings in CHF on the echocardiogram include: hypokinesia; valvular insufficiency; and enlargement of all heart chambers.

Other Imaging findings

The abreugraphy is a smaller variant of the chest X-ray that allows the identification of lung abnormalities that may suggest the diagnosis of TB. With the decrease of incidence of TB, the abreugraphy is no longer recommended in most countries for low-risk populations. However, depending on the screening resources of each country, it may be used for the screening of high-risk groups, such as HIV-positive patients and alcoholics.

Other Diagnostic Studies

Because of difficulties with the Tuberculin skin test, many laboratory methods of diagnosis are emerging.

Treatment

Medical Therapy

If there is a high probability of infection, presumptively treat the patient even if the stain is negative, while waiting for the culture results. The patient should be brought back in a few weeks. Patients usually feel better a few weeks post-treatment. Patients must be monitored for adverse effects and treatment failure. In the U.S., all TB is tested for drug resistance.

Special conditions

Medical therapy for tuberculosis in special conditions include HIV co-infection and extra pulmonary manifestations. Different approaches are taken for patients taking ART and those who do not take ART. Although WHO recommends the same drug regimen for pulmonary and extrapulmonary manifestations, various stages of skeletal tuberculosis are managed differently. For patients with renal or liver diseases, the first line of drugs are substituted with second-line drugs to prevent complications.

Drug-resistant

Drug-resistant tuberculosis is caused by M. tuberculosis organisms that are resistant to at least one first-line anti-TB drug. Multidrug-resistant TB (MDR TB) is resistant to more than one anti-TB drug and at least isoniazid (INH) and rifampin (RIF). Treatment should be started with an empirical treatment of at least 4 drugs based on expert advice as soon as drug-resistant TB disease is suspected.

Children

Tuberculosis in children aged 15 years or younger is a public health problem of special significance because it is a marker for recent transmission of TB. Infants and young children are more likely to develop life-threatening forms of tuberculosis, such as miliary TB or TB meningitis. Screening in children is very important, as the clinical manifestations are usually poor or non-specific. History of close contact with tuberculosis patients has an important role in the diagnosis of TB in children. The treatment is similar to adults, with adjusted dosing according to the child's weight.

Surgery

Surgery may be necessary, especially to drain abscesses , empyema, venticular shunt in tubercular meningitis, surgical resection of tissues affected in abdominal tuberculosis, stabilize the spine in case of Pott's disease, lobectomy, pneumonectomy, pericardiocentesis or surgical repair of pericardium.

Primary Prevention

Primary prevention in tuberculosis is targeted to avoid disease transmission and infection of healthy individuals. The BCG vaccine is used in children susceptible to TB infections, such as children living in endemic areas or having close contact with a confirmed case of TB. Several preventive measures are used to avoid the transmission of the mycobacteria, such as respiratory isolation, use of respiratory masks among health-care professionals, and advising respiratory hygiene and cough etiquette.

Secondary Prevention

Secondary prevention for tuberculosis includes methods for screening and early diagnosis, such as tuberculin skin test (TST) and IGRAs; and to guarantee the correct treatment regimen at the right time to prevent disease progression.

Cost effectiveness of therapy

Treatment of tuberculosis must be analyzed for relative cost effectiveness of inpatient and outpatient models of care as it will benefit regions where tuberculosis is highly prevalent. Unless there is severe complications it is highly recommended to treat the TB patient in ambulatory care rather than inpatient services.

Future or investigational therapy

Since new drug-resistant tuberculosis has been emerging, the role of future therapies is vital in curbing outbreaks. The new drugs should be more effective than the current regimen and a few drugs in clinical trials have been showing good results.

References

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