Tuberculosis
There are two states of Tuberculosis (TB). The latent TB infection occurs when
the TB bacteria are inhaled but the body is able to stop the bacteria from growing. People
with the latent form have no symptoms, can’t spread the bacteria to others, but can
develop the disease if they do not receive treatment (CDC: Questions and Answers About
TB, 2005). The second state of tuberculosis is the active TB disease, which will be the
main focus of this research.
Causative Agent:
The cause of tuberculosis in humans is the Mycobacterium tuberculosis (rarely M.
bovis and M. avium cause TB in humans but more commonly other animals)
(Microbiology TexTBook, 2005). M. tuberculosis is large, thin, slow growing bacilli,
with a cell wall made of a waxy substance called mycolic acid which makes the cell less
permeable (Ellis and Zabrowarny, 1997). This permeability barrier makes the cell repel
stains, causing Gram stains to show a weak positive, or to show up white; so typically an
alternative (acid-fast) stain is used instead (Microbiology TexTBook, 2005). The cells
are arranged in “cords” (long lines that are placed end to end) (Microbiology TexTBook,
2005).
The knowledge of bacterial metabolism is still developing, but it is known that M.
tuberculosis can adapt their metabolism to the available sources within the host’s tissues;
causing the bacteria to become firmly planted within the host (Fritz et al., 2002). The
metabolism of fatty acids as a source of carbohydrates is necessary for the growth of M.
tuberculosis. While most of the bacteria prefer to have access to oxygen, they can adapt
to anaerobic conditions by using nitrate to replace oxygen in the production of ATP
(Fritz, et al., 2002).
History:
The first known case of recorded pulmonary TB occurred between 668-626 BC.
This record was found in the library of King Assurbanipal of Assyria the following is an
extract: “The patient coughs frequently, his sputum is thick and sometimes contains
blood. His breathing is like a flute. His skin is cold, but his feet are hot. He sweats
greatly and his heart is much disturbed. When the disease is extremely grave, he suffers
from diarrhea” (Harms, 1997). Even earlier, are records of another form TB such as M.
bovis which commonly affects cows (Harms, 1997). Research has suggested that M.
bovis was the first to begin causing disease humans after the farming of cattle began
around 8000-4000 BC (Harms, 1997). It has been hypothesized that around 1000 BC M.
tuberculosis adapted itself to humans from the M. bovis strain (Harms, 1997). In the
seventeenth century Sylvius recorded anatomical descriptions of TB and also noted
pathological changes in the lungs of a infected TB patient (Harms, 1997). He noted that
the lungs underwent distinct changes and even noted tubercles which were consistent to
TB patients (Harms, 1997). After the turn of the eighteenth century, a physician in
England by the name of Benjamin Marten postulated that the disease was caused by
“minute living creatures” and further speculated that “It may be therefore very likely that
by an habitual lying in the same bed with a consumptive patient [consumption was the
name by which TB was known at the time], constantly eating and drinking with him, or
by very frequently conversing so nearly as to draw in part of the breath he emits from the
lungs, a consumption may be caught by a sound person…I imagine that slightly
conversing with consumptive patients is seldom or never sufficient to catch the disease”
(Harms, 1997). Confirmation of Marten’s speculation would not come until eighteensixty-five when TB was shown to be able to pass from humans to cattle to rabbits by Dr.
Jean-Antoine Villemin (Harms, 1997). By the end of the nineteenth century Robert Koch
brought TB to light by using a new staining technique that made viewing M. tuberculosis
possible (Harms, 1997).
Epidemiology:
Current statistics show that over 1/3 of the world’s population is infected (latent
and active stages) with TB, of the infected around 3 million people die every year from
active TB (Microbiology TexTBook, 2005). In is estimated that for every single minute
that passes 60 people become infected somewhere in the world (Harms, 1997). If the rate
infection remains the same, over the next 10 years over 30 million people could die from
TB (Harms, 1997). South East Asia accounts for a third of world wide cases
(http://w3.whosea.org/TB/ magnitude.htm, 2005). Around two thousand people die every
day resulting from TB infections in South East Asia that is around _ of a million a year
(http://w3.whosea.org /TB/magnitude.htm, 2005).
Humans remain the only reservoir for M. tuberculosis but M. bovis (has it’s
reservoir in cattle) will also sometimes infect humans through un-pasteurized milk and
cause extrapulmonary TB (Microbiology TexTBook, 2005). Cases of TB rose from 1985
to 1992 which have been attributed to AIDS (Microbiology TexTBook, 2005). AIDS
patients are excellent incubators of M. tuberculosis but also M. bovis and M. avium (bird
TB) which takes advantage of their weekend immune system (http://
texTBookofbacteriology.net/tuberculosis.html , 2005). TB remains the most prevalent
infectious killer among AIDS patients about 1/3 of them will become infected with it
(Harms, 1997).
Pathology:
The infection of tuberculosis begins when a person inhales infected bacilli that are
released from the lungs of an infected person (it can take as little as one droplet to
become infected) (Kaplan et al., 2003). Once the bacteria reach the lungs the alveolar
macrophages (cells found in the lungs that destroy pathogens) attempt to destroy the
bacteria. Two to three weeks after infection the immune system forms tubercles (lesions)
that contains the mycobacteria (Microbiology TexTBook, 2005). Ninety percent of the
infections stop here and lay dormant (for an indefinite period of time) possibly never
going on to be a detectable active disease (Kaplan et al., 2003).
If the bacteria do not lay dormant, the bacteria continue to grow until the tubercles
invade other portions of the lung and active tuberculosis begins (Microbiology
TexTBook, 2005). Once, in the active stage, cell death (necrosis) occurs and cavities are
formed in the lungs (Microbiology TexTBook, 2005). The necrosis is believed to be
caused as a result of the response of the immune system by releasing cytokine (a protein
that acts as a mediator in the immune response system) at toxic levels and the release of
proteolytic enzymes (enzyme that catalyzes the splitting of proteins) (Kaplan, et al.,
2003). In addition the growth of M. tuberculosis is accelerated if the bacteria have
increased access to oxygen which is why the infection normally occurs in the lungs
(Kaplan et al., 2003).
Although tuberculosis normally affects the lungs it can spread to other parts of the
body like the brain, blood, bones, glands, etc. (Questions and Answers About TB, 2005).
Symptoms include a cough that lasts longer than two weeks, pain in the chest, coughing
up blood or sputum (phlegm from deep inside the lungs). Other symptoms include
weakness, weight loss, no appetite, chills, fever, and night sweats (Questions and
Answers About TB, 2005).
Response and Treatment
The immune system reacts to Tuberculosis (TB) in two different ways depending
on weather TB is in the active or latent phase. When the TB germs are latent in the body
they are considered infections. After they have entered the body the immune system
reacts by building a wall around them in the way a scab forms over a cut. TB can stay
alive inside these walls for years, or even for a life-time, in a latent state. While the
bacteria live inside these walls they can not be spread from one person to another and
they do not create any harm to the host (www.cpmc.columbia.edu).
When tuberculosis is in an active state it is considered a disease. People who have
a very weak immune system, such as those with a serious illness, aging, or drug and
alcohol abuse are very good candidates to contracting the disease. Shortly after TB enters
the body of someone with a weak immune system the disease begins damaging tissues
and organs. When latent TB becomes active TB, usually do to a weakened immune
system, the bacteria breaks out of the walls and begin to rapidly multiply. People with
active TB are able to treat the disease by taking several different medications either on
their own or with the help from others and also by surgical treatment if antibiotics are
ineffective (www.cpmc.columbia.edu)
People who have active TB are treated with several types of antibiotics due to the
fact that there are a plethora of bacteria to be killed, and also to prevent the bacteria from
becoming resistant to the medications. The most common medications used to cure TB
are, isoniazid, rifampin, ethambutol, pyrazinamide. TB bacteria die very slowly and it
takes at least six months for the medicine to kill all of the TB bacteria. Many people start
feeling better after only a few weeks of treatment even though the TB bacteria are still
alive in their bodies. Since many people start to feel better after only a few weeks of
antibiotic therapy they tend to skip doses of medications or quit taking them all together.
When this happens the TB bacteria will grow again and may keep the individual sick for
a longer period of time. The bacteria may also become resistant to the medications they
were taking, and in that case new and different medications will be prescribed. Patients
with drug resistant TB should be treated with a minimum of two to three drugs to which
their organisms are susceptible. It is very important that the medications are taken exactly
as directed by a nurse or physician, and local health departments offer DOT therapy
which can also help increase the chances of TB to be cured from an individual
(www.cdc.gov, www.respiratory-lung.health-cares.net).
DOT therapy, or directly observed therapy, involves meeting with a health care
worker every day or several times a week. DOT helps in several ways. The health care
worker can help remind those with TB to take their medication and complete treatment.
Also with DOT, medication may only need to be taken two to three times a week rather
than every day (www.cdc.gov).
Surgical treatment of tuberculosis may be used if medications are ineffective all
together. There are three surgical procedures for respiratory TB: pneumothorax, in which
air is introduced into the chest to collapse the lung; thoracoplasty, in which one or more
ribs are removed; and removal of a diseased lung, in whole or in part. According to
health-cares.net it is possible for patients to survive with one healthy lung. Spinal
tuberculosis may result in a severe deformity that can be corrected surgically
(www.repiratory-lung.health-cares.net).
There have been several preventative measures that have been developed in order
to lesser the chances of an individual contracting TB. These measures include strict
standards for ventilation, air filtration, and isolation methods in hospitals, medical and
dental offices, nursing homes and prisons. If someone is believed to have been in contact
with someone infected with TB preventative antibiotic treatment may have to be given.
There has also been a vaccine developed called Bacillus Camille Guerin (BCG) which is
useful in preventing certain types of tuberculosis, although it’s effectiveness is variable.
There has not yet been a vaccine that is truly one-hundred percent effective against adult
forms of the disease (www.respiratory-lung.health-cares.net).
Many countries use BCG vaccine as part of their TB control programs, especially
for infants. The statistics for preventing serious forms of TB (e.g. meningitis), using the
BCG vaccine in infants, is fairly high at greater than eighty percent. In adults, however,
the effectiveness ranges from zero to eighty percent. The vaccination does not prevent
infection of TB, but it does strengthen the immune system of first-time tuberculosis
patients. As a result, serious complications are less likely to develop. BCG is used more
widely in developing countries in comparison to the U.S. The effectiveness of the vaccine
is still being studied; it is not clear whether the vaccine’s effectiveness depends on the
population in which it is used or on variations of its formulation (www.respiratorylung.health-cares.net).
Social, Economic, & Political Issues:
The social and economic issues of Tuberculosis are vast. The cost of TB is
difficult to estimate because 80% of the victims are 15-49 years old which is the most
financial productive time of their lives, and a patient that isn’t diagnosed or cured loses
approximately an entire year of work (www.results.org, 2005). By curing a patient not
only is their productivity restored but additional TB deaths are prevented, which leads to
a large positive economic impact (WHO: DOTS Experiences So Far, 2005). For example
the economic impact in India from tuberculosis is at least a $372 million yearly loss; but
if treatment plans are implemented throughout the country it is estimated to have an
economic gain of $10 billion (WHO: DOTS Experiences So Far, 2005). Where as lack
of treatment or inconsistent treatment leads to the drug resistant form of TB, which is
more difficult and cost prohibitive to treat so is normally a death sentence to
impoverished countries (www.results.org, 2005).
In the United States between 1992 and 1996 there was a tuberculosis epidemic
that New York City alone spent $700 million to stop. Yet, people of the United States
feel that tuberculosis is a disease of the past and something not to worry about, even
though 15 million people in the U.S. are infected with the bacteria (the rates of TB are
highest for minorities in the U.S. because of socio-economic issues such as high
unemployment, low median income, and poor living conditions) (www.results.org,
2005). In addition, tuberculosis is a major problem in developing countries, and there is
no way to seal the borders of the United States from this disease. Yearly there are one
million plus refugees and immigrants that enter the United States, large amounts of
Americans that are traveling to high-risk countries, in addition to the millions of foreignborn travelers that enter the U.S., exposing the population to tuberculosis
(www.results.org, 2005). The only way to effectively control tuberculosis in the United
States is to control it worldwide (www.results.org, 2005).
Currently the World Health Organization recommends that the most effective way
to combat tuberculosis is by further implementing the Directly Observed Therapy Short
Course (DOTS). This strategy works by ensuring that patients are diagnosed and
monitored during treatments, which stops TB at the source preventing the spread of the
bacteria (WHO: DOTS Strategy, 2005). Another tangible benefit of tuberculosis
treatment is that it is a cost-effective way to raise the quality of life for AIDS patients (for
example a person with HIV in a developing country that contracts TB has a survival time
of 5-6 weeks, but with TB treatment survival rates are 2-5 years (www.results.org, 2005).
There are five main obstacles to overcome for DOTS to expand: shortages of
trained staff; lack of political commitment; weak laboratory services; and lack of
management of drug resistance TB. To address these challenges, tuberculosis needs to be
a high priority with national policy makers and governments. Practices that would
employ DOTS expansion include: providing financing for administrative support of
DOTS implementation and to increase the manufacturing of drug treatments; supporting
an increase of manpower to supervise and sustain DOTS; enhancing inter-country
collaboration to maximize benefits from private donors and grants; and promoting
operational research to continually advance strategies. By implementing these strategies
it means to take funds, manpower and attention from other diseases; however the benefits
of implementing the DOTS program can save millions of lives over the next 20 years in
an extremely cost effective manor (WHO: DOTS Strategy, 2005).
Literature Cited
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www.cpmc.columbia.edu/resources/tbcpp/tbcure.html
Center for Disease Control. July 8, 2005. Questions and Answers About TB 2005.
http://www.cdc.gov/nchstp/TB/faqs/qa_introduction.htm.
Division of Tuberculosis Elimination. July 15, 2005. Latent and Active TB Spread.
www.cdc.gov/nchstp/tb/faqs/qa_intr.html
Ellis and Zabrowarny. July 13, 2005. Stain for Acid Fast Bacilli.
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Harms, Jerome. 1997. Tuberculosis: Captain Death.
http://www.bact.wisc.edu/Bact330/lectureTB
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Kenneth Todar University of Wisconsin-Madison Department of Bacteriology.
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http://texTBookofbacteriology.net/tuberculosis.html
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http://w3.whosea.org/TB/magnitude.htm
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http://w3/whosea.org/EN/Section10/Section186/Section190.htm.
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http://w3/whosea.org/EN/Section10/Section186/Section190_451.htm.