Tuberculosis Prognosis

Progression from TB infection to TB disease occurs when the TB bacilli overcome the immune system
defenses and begin to multiply. In primary TB disease15% of casesthis occurs soon after infection.
The risk of reactivation increases with immunosuppression, such as that caused by infection with HIV. In
patients co-infected with ''M. tuberculosis'' and HIV, the risk of reactivation increases to 10% per year.
Roughly a third of the world's population has been infected with ''M. tuberculosis'', and new infections occur
at a rate of one per second. However, not all infections with ''M. tuberculosis'' cause TB disease and many
infections are asymptomatic. In 2007, an estimated 13.7 million people had active TB disease, with 9.3
million new cases and 1.8 million deaths; the annual incidence rate varied from 363 per 100,000 in Africa to
32 per 100,000 in the Americas. Tuberculosis is the world's greatest infectious killer of women of
reproductive age and the leading cause of death among people with HIV/AIDS.
The rise in HIV infections and the neglect of TB control programs have enabled a resurgence of
tuberculosis. The emergence of drug-resistant strains has also contributed to this new epidemic with, from
2000 to 2004, 20% of TB cases being resistant to standard treatments and 2% resistant to second-line drugs.
The rate at which new TB cases occur varies widely, even in neighboring countries, apparently because of
differences in health care systems.
In 2007, the country with the highest estimated incidence rate of TB was Swaziland, with 1200 cases per
100,000 people. India had the largest total incidence, with an estimated 2.0 million new cases.. In developed
countries, tuberculosis is less common and is mainly an urban disease. In the United Kingdom, the national
average was 15 per 100,000 in 2007, and the highest incidence rates in Western Europe were 30 per 100,000
in Portugal and Spain. These rates compared with 98 per 100,000 in China and 48 per 100,000 in Brazil. In
the United States, the overall tuberculosis case rate was 4 per 100,000 persons in 2007.
The incidence of TB varies with age. In Africa, TB primarily affects adolescents and young adults. However,
in countries where TB has gone from high to low incidence, such as the United States, TB is mainly a
disease of older people, or of the immunocompromised .
There are a number of known factors that make people more susceptible to TB infection: worldwide the
most important of these is HIV. Co-infection with HIV is a particular problem in Sub-Saharan Africa, due to
the high incidence of HIV in these countries. Smoking more than 20 cigarettes a day also increases the risk
of TB by two to four times. Diabetes mellitus is also an important risk factor that is growing in importance
in developing countries. Other disease states that increase the risk of developing tuberculosis are Hodgkin
lymphoma, end-stage renal disease, chronic lung disease, malnutrition, and alcoholism. Although a causal
link is not proved by this data, this increased risk could be caused by micronutrient deficiencies: possibly
iron, vitamin B12 or vitamin D. Globally, the severe malnutrition common in parts of the developing world
causes a large increase in the risk of developing active tuberculosis, due to its damaging effects on the
immune system. Along with overcrowding, poor nutrition may contribute to the strong link observed
between tuberculosis and poverty.

Prognosis
With appropriate antibiotic therapy, only 10% of patients will die (Lessnau). Individuals with pulmonary TB are
usually not contagious after 10 to 14 days of drug treatment. However, a follow-up sputum analysis should be
performed to make sure there is no longer any danger of transmission. Treatment should be continued for 3 months
after sputum cultures are negative for the TB bacteria. Drugs used to treat TB however, have many side effects and
should be constantly monitored.
Relapse of TB often occurs as a result of noncompliance with treatment. With complete and proper treatment, relapse
rates are less than 5% (Lessnau).
Individuals infected with resistant strains of TB have a lower cure rate. Strains of TB bacteria resistant to two or more
drugs (multidrug-resistant) can have a higher reported mortality rate.

Follow-up
Further Inpatient Care

Hospitalized patients with suspected or documented tuberculosis (TB) must be placed in appropriate
isolation. This includes a private room with negative pressure and adequate air exchanges. Persons
entering the room must wear masks or respirators capable of filtering droplet nuclei.

Worldwide, TB rates are consistently higher among health care workers than in the general
population; infection-control measures yield a significant impact in high-income countries but less
impact in low- and middle-income countries.18

Patients with TB should remain in isolation until sputum becomes smear-negative; however, patients
should not ordinarily be kept in the hospital for the sole purpose of providing isolation. Special
arrangements are necessary for patients with TB who live with children, individuals infected with
HIV, or patients returning to a closed-group setting (eg, nursing home, correctional facilities,
residential facility, homeless shelter).
Further Outpatient Care
Patients diagnosed with active TB should undergo sputum analysis for M tuberculosis weekly until
sputum conversion is documented. Monitoring for toxicity includes baseline and periodic liver
enzymes, CBC count, and serum creatinine.
In addition, patients with TB who are receiving pyrazinamide should undergo baseline or periodic
serum uric acid assessments, and patients with TB who are receiving long-term ethambutol therapy
should undergo baseline or periodic visual acuity and red-green color perception testing. The latter
can be performed with a standard test such as the Ishihara test for color blindness.
Deterrence/Prevention

Patients with a clinically significant result on tuberculin skin testing or positive IGRA result (see
Other Tests) should receive a course of therapy once active infection and disease is ruled out.
Guidelines published by the CDC in 2000 now refer to this as treatment of latent TB. The
recommended regimens are listed below:
o Isoniazid daily for 9 months
o Isoniazid twice weekly for 9 months (administered as DOT)
o Isoniazid daily for 6 months (should not be used in patients with fibrotic lesions on chest
radiography, patients with HIV, or children)
o Isoniazid twice weekly for 6 months (administered as DOT; should not be used in patients
with fibrotic lesions on chest radiography, patients with HIV, or children)
o Rifampin daily for 4 months
o Rifampin plus pyrazinamide daily for 2 months (This regimen is no longer recommended
because of an increased risk for liver toxicity.)

Children should receive isoniazid for 9 months. In addition, children younger than 5 years who have
close contact with a person who has active TB should be started on isoniazid, even if results on skin
testing are negative; preventive therapy can be stopped if results on repeat skin testing are negative
2-3 months after last contact with a culture-positive source case.

Patients exposed to MDR-TB may be administered ethambutol plus pyrazinamide for 6-12 months or
pyrazinamide plus levofloxacin for 6-12 months; the index isolate should be susceptible to all drugs
used.

Recommended regimens in patients with HIV infection include rifampin alone daily for 4 months or
isoniazid, daily or twice weekly, for 9 months. Patients on antiretroviral therapy may need rifabutin
instead of rifampin because of potential drug interactions. The 2-month combination of pyrazinamide
plus rifampin is no longer recommended.

The BCG vaccine continues to be used throughout much of the world and provides protection mostly
until early childhood. Immunity begins to wane as early as 3 months after administration.19
Complications
Late complications of pulmonary TB include relapse, aspergilloma, bronchiectasis, broncholithiasis,
fibrothorax, and possibly carcinoma. A copy of the chest radiograph at the time of completion of
therapy should be provided to the patient to facilitate the diagnosis of late complications.

o
o

The relapse rate following appropriate completed therapy is only 0-4% and occurs within the
first 2 years after completion. Therefore, re-treatment is usually unnecessary, especially after
DOT.
Aspergilloma is a fungus ball that develops in a residual lung abnormality (eg, pneumatocele,
bulla, bleb, cyst). It may appear as a crescent sign on chest radiographs. Other superinfections
may manifest with an air-fluid level and often contain mixed bacteria, including anaerobes.
Hemoptysis is the most common late complication. Broncholithiasis is the result of
spontaneous lymph node migration into the bronchial tree and may be associated with
postobstructive pneumonia or esophageal perforation. Bronchiectasis may progress to chronic
bronchitis; bleeding from submucosal bronchial veins is usually self-limited.
Fibrothorax is the development of trapped lung due to pleural fibrosis and scarring.
The risk of carcinoma is controversial but should be considered with newly developing
clubbing.

Prognosis
Among published studies involving DOTS treatment, the rate of recurrence ranges from 0-14%. 20 In
countries with low TB rates, recurrences usually occur within 12 months of treatment completion and are
due to relapse.21 In countries with higher TB rates, most recurrences after appropriate treatment are probably
due to reinfection rather than relapse.22
Patient Education
For excellent patient education resources, visit eMedicine's Bacterial and Viral Infections Center. Also, see
eMedicine's patient education article Tuberculosis.
Miscellaneous
Medicolegal Pitfalls
Laws vary from state to state, but communicable-disease laws typically empower public health
officials to investigate suspected cases of tuberculosis (TB), including potential contacts. In addition,
patients may be incarcerated for noncompliance with therapy. For example, in the Denver Metro
Tuberculosis Clinic from 1984-1994, 5% of patients were incarcerated for noncompliance and an
additional 5% who were lost to follow-up before completing therapy would have been candidates for
incarceration.
Special Concerns
Pregnancy
o
Pregnancy provides an opportunity to screen for TB; all pregnant women can undergo
tuberculin skin testing. If skin-testing results are positive, chest radiography can be performed
with lead shielding (the amount of radiation exposure of a single chest radiograph has been
compared to that incurred on a regular flight from New York to Los Angeles). Chest
radiography should not be delayed during the first 3 months of pregnancy in patients with
suggestive symptoms.
o
Active TB should be treated, even in women in the first stage of pregnancy. Isoniazid,
rifampin, and ethambutol may be used. In the United States, pyrazinamide is reserved for
women with suspected MDR-TB. Elsewhere in the world, pyrazinamide is commonly used in
pregnant women with TB.

Preventive treatment is recommended during pregnancy, especially in the following

situations:
Pregnant women with a positive tuberculin skin test result who are HIV seropositive
or who have behavioral risk factors for HIV infection but decline HIV testing

Pregnant women with a positive tuberculin skin test result who have been in close
contact with a patient who is smear-positive for pulmonary TB
Pregnant women who have had a documented tuberculin skin test conversion in the
past 2 years
o
Pregnant women are at an increased risk for isoniazid-induced hepatotoxicity and should
undergo monthly ALT monitoring while on treatment. This risk continues 2-3 months into the
postpartum period. Pyridoxine should also be administered to pregnant women receiving
isoniazid. Breastfeeding can be continued during preventive therapy. Many experts
recommend supplemental pyridoxine to the breastfed infant.
Tuberculosis in children
o
TB in a child is a sentinel event indicating recent transmission, and contacts should be
evaluated to find the source case as soon as possible. Children do not commonly infect other
children because they rarely develop cough and sputum production is scant. However, cases
of child-child and child-adult TB transmission are well-documented.
o
Chest radiographs in children with TB may show only hilar lymphadenopathy or a patchy
infiltrate. Most children with TB can be treated with isoniazid and rifampin for 6 months,
along with pyrazinamide for the first 2 months if the culture from the source case is fully
susceptible. Gastric aspirates or biopsies are not necessary if positive cultures have been
obtained from the source case.
o
In children younger than 5 years, the potential for development of fatal miliary TB or
meningeal TB is a significant concern. TB disease is uncommon in children aged 5-15 years
(the golden age of childhood).
o
Isoniazid tablets may be crushed and added to food. Isoniazid liquid without sorbitol should
be used to avoid osmotic diarrhea, causing decreased absorption. Rifampin capsules may be
opened and the powder added to food. If rifampin is not tolerated, it may be taken in divided
doses 20 minutes after light meals.
o
Ethambutol is often avoided in young children because of difficulties monitoring visual
acuity and color perception. However, studies show that ethambutol (15 mg/kg) is well
tolerated and can prevent further resistance if the child is infected with a resistant strain.
Human immunodeficiency virus
o
Individuals infected with HIV are at an increased risk for TB, beginning within the first year
of HIV infection.23 Based on historical data, the initiation of antiretroviral therapy decreases
the risk of developing TB in these patients.24
o
Patients with TB must be tested for HIV, and patients with HIV need periodic evaluation for
TB with tuberculin skin testing and/or chest radiography. Patients with HIV and a positive
tuberculin skin test result develop active TB at a rate of 3-16% per year.
o
Patients with TB and HIV are more likely to have disseminated disease and less likely to
have upper-lobe infiltrates or classic cavitary pulmonary disease. Patients with a CD4 count
of less than 200/L may have mediastinal adenopathy with infiltrates.
o
Treatment regimens for active or latent TB in patients with HIV infection are similar to the
treatment of individuals who are HIV negative, but dose adjustments may be necessary. 25 The
most significant differences involve the avoidance of rifampin in patients who are on protease
inhibitors. Rifabutin may be used in place of rifampin in such patients.
o
Patients with HIV and TB may develop a paradoxical response when starting antiretroviral
therapy. This response has been attributed to a stronger immune response to M tuberculosis.
Clinical findings include fever, worsening pulmonary infiltrates, and lymphadenopathy.
Tumor necrosis factor-alpha (TNF-a) antagonists have been associated with a significantly increased
risk for TB.26 Reports have included atypical presentations, extrapulmonary and disseminated
disease, and deaths. Patients scheduled to begin therapy with a TNF- antagonist should be screened
for latent TB and counseled regarding the risk of TB.