Tuberculosis

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 Tuberculosis
>>> Tuberculosis (TB) is caused by a bacterium called Mycobacterium
tuberculosis. The bacteria usually attack the lungs, but TB bacteria can attack
any part of the body such as the kidney, spine, and brain.

Not everyone infected with TB bacteria becomes sick. As a result, two TB-
related conditions exist: latent TB infection (LTBI) and TB disease. If not treated
properly, TB disease can be fatal.

According to WHO report, globally about 10 million active tuberculosis cases,

resulting in about 1.6 million deaths, further aggravated by drug-resistant
tuberculosis and/or comorbidities with HIV and diabetes are present.
 Epidemiology and Etiology
Roughly one-third of the world’s population is infected and drug resistance is
increasing in many areas.

The majority of cases worldwide are found in South-East Asia and Africa. In the
United States, about 13 million people have latent TB infection (LTBI),
evidenced by a positive skin test (purified protein derivative [PPD]) but no signs
or symptoms of disease.

The PPD is the antigen derived from Mycobacterium tuberculosis used to

determine the presence of an immune response in patients with previous
exposure. Patients testing positive have roughly a 1 in 10 chance of active
disease during their lives, with the greatest risk in the first 2 years after infection.
 Risk Factors for Infection
 Location and Place of Birth
 Race, Ethnicity, Age, and Gender
 Risk Factors for Disease
Once infected, a person’s lifetime risk of active TB is about 10%, with about half
this risk during the first 2 years.

 Young children, the elderly, and immunocompromised patients have greater

risks.
 HIV is the most important risk factor for active TB because the immune deficit
prevents patients from containing the initial infection.
 HIV-infected patients with M. tuberculosis infection are roughly 100 times
more likely to develop active TB than normal hosts.

TB is caused by M. tuberculosis, a rod-shaped thin aerobic bacterium. It

presents either as LTBI or as progressive active disease. The latter typically
causes progressive destruction of the lungs, leading to death in most patients
who do not receive treatment.
 Pathophysiology
M. tuberculosis is transmitted from person to person by coughing or any other
aerosol producing activities such as sneezing.

This produces small particles known as droplet nuclei that float in the air for long
periods of time. Primary infection usually results from inhaling droplet nuclei that
contain M. tuberculosis.

The progression to clinical disease depends on three factors:

 Number of M. tuberculosis organisms inhaled (infecting dose)
 Virulence of these organisms
 Host’s cell-mediated immune response

If pulmonary macrophages inhibit or kill the bacilli, the infection is aborted.

If not, M. tuberculosis eventually spreads throughout the body through the

bloodstream.
 Pathophysiology
T lymphocytes become activated over the course of 3 to 4 weeks, producing
interferon-γ (INF-γ) and other cytokines. These stimulate microbicidal
macrophages to surround the tuberculous foci and form granulomas to prevent
further extension.

A granuloma is a nodular aggregation of mononuclear inflammatory cells formed

when the immune system attempts to wall off foreign substances. At this point,
the infection is largely under control, and bacillary replication falls off
dramatically.

Any remaining mycobacteria are believed to reside primarily within granulomas

or within macrophages that have avoided detection and lysis. Over 1 to 3
months, tissue hypersensitivity occurs, resulting in a positive PPD.
 Pathophysiology
Approximately 95% of individuals with an intact immune system will enter into
this latent phase. Progressive primary disease occurs in roughly 5% of patients,
especially children, the elderly, and immunocompromised patients.

This presents as a progressive pneumonia and frequently spreads, leading to

meningitis and other severe forms of TB, often before patients develop positive
(PPD) or interferon-γ release assays.

About 10% of infected patients develop reactivation TB, with half occurring in
the first 2 years after infection. Reactivation TB results when a previously
“dormant” focus is reactivated and causes disease.

Progression involves the development of caseating granulomas as a result of a

vigorous immune response.
 Pathophysiology
Liquefaction leads to local spread and a pulmonary cavity results. This provides
a portal to the airways and subsequently ambient air that enhances person-to-
person spread. Bacterial counts in the cavities can be as high as 108/mL
(1011/L) of cavitary fluid.

Caseating granulomas, regardless of location, can spread tubercle bacilli and

cause symptoms. Because of muted or altered symptoms, the diagnosis of TB is
difficult and often delayed in immunocompromised hosts.

HIV-infected patients may present with only extrapulmonary TB, which is

uncommon in HIV-negative persons. A widely disseminated form of the disease
called miliary TB can occur, particularly in children and immunocompromised
hosts. It can be rapidly fatal and immediate treatment is required.

As CD4+ lymphocytes multiply in response to the mycobacterial infection, HIV

multiplies within these cells and selectively destroys them.
 Clinical Presentation and Diagnosis
The classic symptoms of Tuberculosis are:
• Fever
• Night sweats
• Weight loss
• Fatigue
• Productive cough

Onset may be gradual, and the diagnosis is easily missed if the symptoms are
muted.
Progressive pulmonary disease leads to cavitary lesions visible on x-ray.
Physical examination is nonspecific but may be consistent with pneumonia.
Dullness to chest percussion, rales, and increased vocal fremitus may be
observed on examination.
Laboratory data often are uninformative, but a modest increase in the white
blood cell (WBC) count with a lymphocytic predominance can be seen.
Clinical Presentation and Diagnosis
a Other combinations may be appropriate in certain circumstances; additional details are provided in
the section “Recommended Treatment Regimens.”
b When DOT is used, drugs may be given 5 days per week and the necessary number of doses
adjusted accordingly. Although there are no studies that compare 5 with 7 daily doses, extensive
experience indicates this would be an effective practice. DOT should be used when drugs are
administered < 7 days per week.
c Based on expert opinion, patients with cavitation on initial chest radiograph and positive cultures at
completion of 2 months of therapy should receive a 7-month (31-week) continuation phase.
d Pyridoxine (vitamin B6), 25–50 mg/day, is given with INH to all persons at risk of neuropathy (eg,
pregnant women; breastfeeding infants; persons with HIV; patients with diabetes, alcoholism,
malnutrition, or chronic renal failure; or patients with advanced age). For patients with peripheral
neuropathy, experts recommend increasing pyridoxine dose to 100 mg/day.
e Alternatively, some US tuberculosis control programs have administered intensive-phase regimens 5
days per week for 15 doses (3 weeks), then twice weekly for 12 dose.

DOT, directly observed therapy; EMB, ethambutol; HIV, human immunodeficiency virus; INH,
isoniazid; PZA, pyrazinamide; RIF, rifampin.
Centers for Disease Control and Prevention. Treatment of Tuberculosis, American Thoracic Society,
CDC, and Infectious Diseases Society of America.
 HEENT: Head, eyes, ears, nose, and throat
PERRLA: Pupils equal, round, and reactive to
light and accommodation
EOMI: Extraocular movements (or muscles)
intact
JVD: Jugular venous distension
Supple: Flexible

RRR: Regular rate and rhythm; BS: Bowel sounds

A&O×3: awake (or alert) and oriented to person, place, and time
A&O×4: Above 3 plus situation