Overview
Tuberculosis
(TB) in humans most often occurs as a result of infection
by the bacilli Mycobacteria tuberculosis. These bacilli
are part of a larger suite of mycobacteria known as the tuberculosis complex.
Other members of this complex, including M. africanum and M. bovis can also
cause tuberculosis in humans, but neither of these latter two occurs in Canada.
M. bovis, or "Bovine tuberculosis"
caused by the ingestion of unpasturised milk, has largely been eradicated.
Mycobacterium are so named because their surface
is covered with mycolic acid, a substance that makes these bacilli very difficult
to stain or track, as the acid coating effectively repels most other substances.
In a sense, this also makes a form of "latent tuberculosis" possible
by allowing the bacilli to remain dormant in a host's body for years, sometimes
decades.
Not all forms of mycobacterium are related to tuberculosis,
and it is important to recognize this in order to avoid confusion. There are
other types of mycobacterium, often simply referred to as the "non-TB
mycobacterium". One of these is M. leprae, known for causing leprosy.
Transmission of Tuberculosis
Tuberculosis (TB) is a contagious disease. When
infected persons cough, sneeze, talk or spit, they propel small minute droplets
of moisture, known as droplet nuclei that have been slowly reduced by evaporation
such that they have a very slow settling rate (0.5mm per second), through
air currents. These droplet nuclei provide a very effective windborne dispersal
method, as a person needs only to inhale a small number of bacilli to become
infected with tuberculosis.
Once infected, tuberculosis bacilli may settle
in virtually any accessible open cavity. Occasionally, tuberculosis may occur
in the gastro-intestinal system or the urinary tract, but the vast majority
of active tuberculosis cases (80%) are pulmonary (in which bacilli settle
in the lung). Given that tuberculosis is dispersed through droplet nuclei
exhaled from the body, it follows that only patients with pulmonary (i.e.
lung-based) tuberculosis are infectious.
Left untreated, each person with pulmonary tuberculosis will infect on average
between 10 and 15 people every year (WHO, 2002).
Manifestations and Effects of TB
Focusing on pulmonary infection, TB infection begins
when the tubercle bacilli multiply in the small air sacs of the lungs. A small
number of bacilli may enter the bloodstream and spread throughout the body,
but the body's immune system, unless severely weakened by external conditions,
usually keeps these wayward bacilli under control. The strength of the host's
immune system is the largest determinant of the severity of what M. tuberculosis
will do once inside a host human body. In most cases (>90%), infection
will not lead to active tuberculosis, as the immune systems of most hosts
will be able to successfully fight off the tuberculosis bacilli, forcing it
into "latentcy" (Kirchner, 1999). However, or the remaining 10 percent
of individuals with depressed immune systems, roughly half will progress to
develop active tuberculosis slowly over time, while the other five percent
will develop active infections almost immediately and can die without proper
treatment (Kirchner 1999).
Treatment
Once diagnosed, patients are kept in isolated for
two weeks. At this time, epidemiological contact tracing begins in order to
determine whether or not the isolated individual has infected others. Upon
diagnoses, if drug therapy is pursued, antibiotics administered include Isoniazid
(INH), Rifampin (RMP), Pyrazinamide
(PZA), Ethambutol (EMP), and
Streptomycin (STREP) (Canadian Lung Association, 2002). These drugs are
provided at no cost to infected patients. In cases where a patient has a strain
of M. Tuberculosis that has developed resistance to particular antibiotics,
combinations of drugs are often administered. Drug therapy lasts for approximately
6-8 months, and it is critical that patients take the prescribed amount of
each medication at the prescribed intervals. If the treatment directions are
not followed precisely, the infected individual risks developing a mutant
strain of TB that is resistant to treatment (New Jersey Medical School, 2002).
In 1986, for example, over a quarter of patients in Canada developed such
a "mutant strain" by not sufficiently following the prescription
directions .
The best means of ensuring that all infected patients
follow the prescribed treatment is Directly Observed
Therapy (DOT), first developed in 1990. This is a process whereby the
ingestion of every dose of medication is directly observed by a health professional,
a process which may last for up to six months. As a result of DOTs, the rate
of drug resistance has lowered to seven percent (Canadian Lung Association,
2002).
Current Issues: Drug Resistance
Tuberculosis, like all living organisms, is capable
of adaptation and evolution. This is an issue for tuberculosis control, as
it explains the emergence of multi-drug resistance. Drug resistance in TB
occurs as a result of spontaneous mutations of M. tuberculosis, mutations
that are independent of the presence/absence of the drug. For example, if
the predominant bacilli were exposed to a single effective anti-TB medication,
the predominant bacilli, sensitive to that drug, are killed. However, the
few drug resistant mutants (likely to be included in a large bacterial population)
will multiply freely given the absence of competition. Since it is very unlikely
that a single bacillus will spontaneously mutate to resistance to more than
one drug, the simultaneous administration of multiple effective drugs will
help to inhibit the multiplication of these resistant mutants. This is why
it is absolutely essential to treat TB patients with the proper treatment
regime, and provides another rationale for directly observed treatment (DOT)
programs.
Current Issues: TB and HIV
As the progression from HIV
to AIDS is based on T-cell
counts and viral load, the presence of tuberculosis in HIV-positive individuals
is of particular note. Kirschener (1999) emphasizes the importance of early
diagnosis of TB amongst HIV positive individuals. He also found that patients
infected with TB and HIV had a much lower initial CD4+ T-cell count than those
infected with only tuberculosis (Krischener, 1999).
Worldwide, the majority of HIV-TB co-infections
are treated only for TB, as antibiotics are less expensive and more readily
available than antiviral drugs. After treatment, Kirschener (1999) found that
the patient's T cell counts rose significantly in both groups (TB only and
those infected with both TB and HIV), but co-infected patients took three
months longer to gradually improve.
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