Download Tuberculosis Tuberculosis (TB) is rare in Australia, but has a

Tuberculosis
Tuberculosis (TB) is rare in Australia, but has a persistent pattern. In Australia, most cases of TB
occur due to reactivation of latent infection, which patients might have from their birth countries1.
Therefore, 85 per cent of TB occurs in people born overseas, with 50 per cent of these cases
occurring in the first five years of residence in Australia1.However, the risk of TB is considered
still higher among people living in poverty, with poor living conditions, malnutrition, and
associated illnesses such as HIV co-infection and/or AIDS, malignancies and diabetes. Moreover,
TB is also rampant in migrants and people who relocate and/or have family disruptions.
TB is caused by the bacteria Mycobacterium Tuberculosis2. It most commonly affects the lungs
but can involve other parts of the body organs e.g.tonsils, lymph nodes, abdominal organs, bones
and joints. TB can be treated, if it is caused by drug-susceptible strains, however, left untreated,
it can be fatal. TB can be transmitted from person to person through airborne droplets when
infectious people cough, sneeze, or spit2.
Epidemiology
World health organization (WHO) in 2009 has reported more than 5.8 million cases of TB
among which 95% of these cases were from developing countries3. WHO estimates that 9.27
million cases of TB occurred in 2007. Of these 9.27 million cases, an estimated 44% were from
India, China, Indonesia, Nigeria and South Africa3. Another predisposing factor is the increasing
number of people with HIV/AIDS, which in turn has increased the incidences of TB infection
among developing countries.
Etiology
Mycobacteria belong to the family Mycobacteriaceae and different pathogenic species belonging
to M. tuberculosis complex. This complex includes mycobacteria M. Bovis, M. Caprae,M.
Africanum and M. Microti4.
M. tuberculosis is thin aerobic, nonspore-forming and rod shaped bacteria. Mycobacteria are
neutral on Gram's staining but have acid fast bacilli, acid fastness is due to its high content of
mycolic acids, long-chain cross-linked fatty acids, and other cell-wall lipids.
TB usually spreads from inhalation of airborne particles containing M. Tuberculosis5. The
bacteria disperse through coughing, sneezing and sputum. It is more likely to affect people with
weaker immune system.
However, on average, patients with pulmonary TB infect about 7 close contacts, but most of
those infected do not develop active disease4. Transmission is enhanced by prolonged or frequent
exposure to a patient who is dispersing large numbers of tubercle bacilli in overcrowded sputum,
in an enclosed space with lack of ventilation. Therefore, people living in poor regions are at
higher risk. Health care professionals are in increased risk if they have close contacts with active
disease patients. However, once treatment for TB starts, cough decreases, organisms become
inactive and within weeks TB is no longertransmittable5.
In developing countries, TB of the tonsils, lymph nodes, abdominal organs, bones and joints are
usually caused by ingestion of milk or milk products contaminated with M. Bovis4. This
transmission route occurs through slaughter of cows that test positive on a tuberculin skin test
and by pasteurization of milk4.
Risk factors:
The main risk categories of TB include:
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Elderly people - due to decline in immunity system.
People with poor nutrition.
People living in unsanitary and crowded places
People with weaker immune system due to HIV infection, diabetes and patient on
chemotherapy.
People who are contact with who have this disease.
Signs and symptoms:
Occasionally patient with active pulmonary TB (moderate or severe disease) may have no
symptoms. However, sometimes they may generally feel unwell, anorexic, fatigued, and may
have weight loss. It may take several weeks to develop specific symptoms4.
The symptoms of pulmonary TB include:
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Cough (In the beginning it may be minimally produce yellow or green sputum, but can
become severe as the disease progresses).
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Dyspnea (Shortness of breath).
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Occasional chest pain with wheezing.
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More susceptible to infections due to decreased immune system.
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Low-grade fever.
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Excessive sweating.
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Weight loss.
Diagnosis
The first stage disease diagnosis of TB is based on patients’ signs and symptoms. It can be
confirmed through a combination of microscopic test for acid-fast bacilli and sputum culture.
These two are the main laboratory test for TB6. For further diagnosis, tests may include:
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Chest x-ray
Tuberculin skin test
Bronchoscopy
CT scan (Chest)
QFT-Gold test to test
Thoracentesis
Figure 1. Chest radiograph showing a right upper-lobe infiltrate and a cavity with an airfluid level in a patient with active tuberculosis2.
Management of tuberculosis:
There are two main aim of tuberculosis drug therpy2

To interrupt TB transmission by rendering patients noninfectious.

Prevent morbidity and death by curing patients infected with TB and prevent the
emergence of drug resistance.
Different countries use different therapies and dosage regimen. The therapies used in Australia
are discussed below is according to therapeutic guidelines.
The most commonly used drugs include:
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Rifampicin
Isoniazid
Ethambutol
Pyrazinamide
Table 2. Rifampicin8
Mechanism of
Derivative of rifamycin B and it inhibits bacterial RNA polymerase.
action
It is bactericidal against rapidly dividing M. tuberculosisand active against
intracellular organisms.
Adverse effects
Arthralgia and myalgia (In the first weeks of treatment), headache,
dizziness, drowsiness, ataxia, confusion, fatigue and weakness.
Monitoring
Liver function tests, serum-creatinine and full blood count before starting
treatment.
Monitor full blood count regularly during the treatment.
Table 3. Isoniazid8
Mechanism of
It inhibits the synthesis of mycolic acids. It is bactericidal against
action
M. tuberculosis and bacteriostatic against resting bacteria.
Adverse effects
Rash, fever, peripheral neuritis, Increased aminotransferases, hepatitis,
acne, tiredness, reduced alertness, raised antinuclear antibodies.
Monitoring
Monitor aminotransferase concentrations at baseline and then each month
as serious hepatotoxicity can occur without symptoms.
Stop isoniazid if aminotransferase concentrations increase to >5 times
ULN (or >3 times ULN with symptoms), or the bilirubin concentration
rises.
Table 4. Ethambutol8
Mechanism of
It may inhibit incorporation of mycolic acid into the mycobacterial cell
action
wall.It is slowly bacteriostatic against M. tuberculosis.
Adverse effects
Optic neuritis, headache, confusion, disorientation, hallucinations, malaise,
vomiting.
Monitoring
Measures CrCl at baseline and regularly during treatment, especially if it
continues for >2 months
Monitor visual acuity and colour vision at start of treatment and each
month if: the dose is >15 mg/kg, treating for >2 months , there is renal
impairment
Table 5.Pyrazinamide8
Mechanism of
action
Bactericidal against M. tuberculosis in acid pH (pH increases as
inflammation decreases).
Adverse effects
Hyperuricaemia, polyarthralgia, nausea
Monitoring
Before treatment obtain full blood count, serum uric acid, creatinine, urea
and liver aminotransferase concentrations.
Stop pyrazinamide if symptomatic hyperuricaemia occurs, monitor serum
aminotransferase concentrations if baseline tests are abnormal, if clinical
symptoms of hepatitis develop or if there is heavy alcohol intake.
There are two types of treatment regimens are used for TB.
1. Daily regimen organisms are susceptible to Isoniazid, Rifampicin and Pyrazinamide; the
patient is able to tolerate all drugs in the regimen; there is full adherence to treatment: there is
no evidence of disseminated or central nervous system TB: extensive cavitation is not present
on the initial chest X-ray: response to treatment is satisfactory.
Isoniazid 300mg (child 10mg/Kg up to 300mg) orally, daily, for 6 month.
Plus
Rifampicin 600mg (adult less than 50Kg: 450mg) (child less than 50Kg: 10mg/Kg up to
450mg; 50Kg or more: 10mg/Kg up to 600mg) orally, daily, for 6 month.
Plus
Ethambutol (adult and child 6 years or more) 15mg/Kg orally, daily, for 2 months.
Plus
Pyrazinamide (adult and child) 25 to 40mg/Kg up to 2g orally, daily, for 2 months.
2. Three-times-weekly regimen (intermittent regimens) regimens are only recommended if
DOT(Directly Observed Treatment) is available and the patient is HIV negative. After at
least 2 weeks of an intensive daily regimen, use:
Isoniazid (adult and child) 15 mg/kg up to 900 mg orally, 3 times weekly for 6 months
Plus
Rifampicin (adult and child) 15 mg/kg up to 600 mg orally, 3 times weekly for 6 months
Plus
Ethambutol (adult and child 6 years or more) 30 mg/kg orally, 3 times weekly for 2 months
Plus
Pyrazinamide (adult and child) 50 mg/kg up to 3 g orally, 3 times weekly for 2 months.
Drug dosages should be reviewed regularly as weight may change significantly during therapy.
Treatment in Children:
Children are particularly susceptible particularly if they have not had BCG vaccination.
Standard short-course therapy is used in children with TB7. Ethambutol should be used in
children less than 6 years of age unless they are resistance to isoniazid and/or rifampicin7.
Treatment for pregnancy and breastfeeding:
Pregnant women with tuberculsis should be treated with standard drug therapy. This is because
the risk of tuberculosis to the fetus is higher than the risk of adverse effects of the drugs.
Breastfeeding should not be discouraged for women on TB treatment. If breastfeeding mother is
taking isoniazid should be given pyridoxine 5 mg daily on the days that the mother receives her
isoniazid dose7.
Infants of mothers with smear-positive pulmonary disease should be closely monitored and
commenced on preventive treatment with isoniazid.
Important point to consider with treating TB patients with HIV, because Rifampicin
interacts with antiretroviral drugs as Rifampicin is an inducer of CYP450 enzymes. Close
monitoring is required if patient is using above combination.
Prevention of tuberculosis:
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Best way to prevent TB is to diagnose and isolate infectious cases quickly and to
administer appropriate treatment until patients are rendered noninfectious7.
Avoid contact to patient who have active TB lesion.
Eat healthy protein rich diet (to build immune system) and get enough sun light (UV rays
from the sunlight are effective in killing TB bacilli).
Whenever planning to travel countries having large number of positive TB cases for
example India, Bangladesh, Pakistan, China, Indonesia, Nigeria and South Africa get
vaccinated against TB.
Consider having BCG vaccination (However, BCG vaccine does not always protect
people from receiving TB). Therefore, if you have symptoms its worth to test TB.
References:
1. Victoria Government Health. Tuberculosis Factsheet. 2005; Available at:
http://www.health.vic.gov.au/ideas/diseases/tb Accessed 12 Aug, 2011.
2. Fauci A. Harrison's Principles of Internal Medicine. 17th ed. ed: Blacklick: McGraw-Hill
companies; 2008.
3. WorldHealthOrganization(2009)."TuberculosisEpidemiology"Avilable at:
http://who.int/entity/tb/publications/global_report/2009/pdf/chapter1.pdf. Accessed12
Aug, 2011.
4. MarckManul. Tuberculosis, Avilable
at:http://www.merckmanuals.com/professional/sec15/ch190/ch190b.html?qt=tuberculosis
&alt=sh. Accessed 12 Aug 2011.
5. Walker R, Whittlesea C. Clinical Pharmacy and Therapeutics. Sydney: Churchill
Livingstone; 2007.
6. Cho S, Brennan PJ. Tuberculosis: Diagnotics. Tuberculosis 2007;87:S14-7.
7. eTG. Tuberculosis. 2010; Available at: http://etg.hcn.net.au.ezproxy1.canberra.edu.au/
Accessed 14 Aug, 2011.
8. Rossi S editor. Australian Medicines Handbook. 2010th ed. SA Australia: Pharmaceutical
Society of Australia; 2010.