Case 1 – tuberculosis
Outbreak investigation, BCG vaccine as preventive method, model of disease, DOTS
I. Tuberculosis
Tuberculosis is a disease caused by germs/bacteria spread from person to person through the air
(airborne). It commonly affects the lungs (a pulmonary disease) but can also affect other parts of the
body.
A. Causes
Tuberculosis (TB) is caused by Mycobacterium Tuberculosis (in humans) and by M.
Bovis in animals/cattle
B. Types
Latent (dormant) TB
• Bacteria cannot replicate but it is still in granulomas
• Cannot infect other people
• Don’t show symptoms
• If the immune system breaks down, the TB bacteria can become active
Active TB
• When the body’s immune system is unable to fight of the TB bacteria
• TB bacteria multiply and spread
• You show the symptoms
Open TB
• When inflammation focus ruptures into airways Bacteria can be spread by
coughing
Miliary TB
• When inflammation focus ruptures into bloodstream: spread of bacteria
throughout entire body
MDR-TB – multidrug resistant TB
• When TB is resistant to at least 2 (I and R) of the anti-TB drugs
• Develops through spontaneous genetic mutation
• Caused by irregular or incomplete treatment
XDR-TB – extensive drug resistant TB
• Resistance of MDR-TB plus one of the other second line drugs
C. Stages of the disease
There are 5 stages of TB:
1. Onset (1-7 Days): The bacteria is inhaled and reach the alveoli
2. Symbiosis (7-21 Days): If the bacteria does not get killed then it reproduces
3. Initial Caseous Necrosis (14-21 Days): Tuberculosis starts to develop when the
bacteria slows down at reproducing, they kill the surrounding non-activated
macrophages and run out of cells to divide in. The bacteria then produces
anoxic conditions and reduces the pH. The bacteria can't reproduce anymore
but can live for a long time.
, 4. Interplay of Tissue-Damaging and Macrophage Activating Immune Response
(After 21 days): Macrophages surround the tubercle but some may be
inactive. Tuberculosis then uses it to reproduce which causes it to grow. The
tubercle can break off and spread around. If it spreads in the blood you can
develop tuberculosis outside the lungs, this is called Miliary Tuberculosis.
5. Liquification and Cavity Formation: The tubercules at one point will liquify,
which will make the disease spread faster, not everyone will get to this stage.
Only a small percent of people will get to this stage.
1-3 is latent, and if it reaches stage 4, it is active.
D. Transmission
Spreads by aerosol droplets (airborne) people with active pulmonary TB disease
cough, sneeze, speak, spit. (Only if we show symptoms we can infect others)
E. Clinical features
1. Symptoms
• Tiredness / Weakness
• Breathlessness
• Night sweats
• Loss of appetite Unintentional weight loss
• Fever
• Chills
• Chest pain
• Chronic coughing
• Sputum production
2. Risk factors
Poverty and HIV infection are major reasons for its persistence. In the native
population, TB is most commonly found among people living in poor
conditions and in deprived areas, especially elderly people and those with
unstable social or psychiatric backgrounds (e.g. streets, prisons, alcoholics,
drugs abusers).
In developing countries, TB is most common among very poor people,
especially those who are malnourished or who also have HIV. As T-cell
function is affected in HIV infected individuals, they have a high risk of TB and
may develop primary, reinfection or endogenous reactivation.
Poverty, poor nutrition and overcrowding tend to occur together. Occupation
exposure can be because of low socioeconomic status (e.g. migrant farm
workers) increased exposure or occupations which specifically predisposition
to TB (miners exposed to silicosis).
Risk factors for infection
• Infectiousness of the patient
o Frequency if coughing and concentration of bacteria in
sputum
o Hygiene
• Degree of exposure
o Duration and distance
, o Living conditions
Risk factors for activation of disease
• Risk of activation decreases in time (largest in first years after
infection)
• HIV infection
• Immunity suppressive drugs weakened immune system
• Diabetes, undernutrition
• Alcoholism
• Genetic susceptibility
Geographical factors
• Place of residence e.g. prisons (malnutrition, poor ventilation,
overcrowding, higher risk of developing HIV through MSM), elderly
homes (due to close contact higher risk, age groups), homeless shelters
• Country of origin (if high incidence rate in population risk for newborn
and children increases) Migration (from high incidence countries to
low incidence countries)
Lifestyle factors
• Poverty – poor housing in terms of crowding leads to increase
transmission and poor nutrition, leads to diminished immunity making
them the two most important factors)
• Health education and access to health care
• Low Socio-Economic Status
F. Epidemiology
In 2011, there were 8.7 million new cases
of active tuberculosis worldwide.
Estimated 310,000 incident cases of
multidrug-resistant TB. More than 60% of
these patients were in China, India,,
Russia, Pakistan and South Africa.
Sub-Saharian Africa has the highest rates
of active TB per capita (driven mostly by
HIV epidemic)
Absolute number of cases is highest in Asia, with India and China having the greatest
burden of disease globally. Due to the fact that globalization took place rather later it
took TB longer to reach continents like Africa or Asia
In USA and most Western countries, the majority of cases occur in foreign-born
residents and recent immigrants from high incidence countries
In 2014: 4.8 per 100,000 people in NL
How to compare the number of TB cases now to 100 years ago? less now: better
hygiene, medicine and surveillance systems
, G. Pathogenesis
1. Infection – primary infection
• Inhaled MTB bacilli reach pulmonary alveoli
• Bacteria are engulfed by macrophages infects alveolar
macrophage and replicate
• Macrophages transport bacteria to lymph nodes
• Antigen presentation of macrophages induces cell-mediated immune
response
• Granuloma is formed white blood cells circle bacteria
• TB becomes clinically apparent not latent but active TB disease
• Affected tissues is replaced by scarring and cavities filled with
necrotic material (Chest X-Ray) can be coughed up and contains living
bacteria and is infectious
• Bacteria trapped in granuloma is in dormant state
• Spreading of bacilli through blood stream TB can develop
everywhere
2. Reactivation of latent TB infection – Secondary pulmonary
• If TB bacilli overcome immune system progress to active Tb
disease (only 10% of TB infections)
II. Diagnosis
A. Chest X-Ray
• Simple and sensitive but unspecific
• Only for pulmonary TB
• If chest x-ray shows abnormalities Tuberculin Skin Tests (TST)
• More expensive
B. Tuberculin skin test (TST)
• To see if you have ever been infected with TB
• Weakened molecules of mycobacterium Bovis bacillus are injected under the
top layer of the skin. If the patient has been exposed to TB bacteria (at least
5-6weeks before the test) the skin will react. It reacts if the patient has
latent, active or been exposed to the BCG vaccine. Induration (local
inflammatory response) is measured 2-3 days later
• For diagnosing Latent
• Pros: cheap, easy to read, fast
• Cons: you don’t know if you have active or latent TB, false-positives (BCG
vaccines), false-negatives (if immune system is suppressed)
C. Ziehl-Nielsen Test (sputum/microbiologic smear)
• More reliable than the tuberculin test but the bacteria are impermeable to
many stains due to the mycolic acid membrane.
• Quick, nearly 100% specific, 50% sensitive
• For active TB
D. Bacteria culture
• Sample of body fluid or tissue taken from the lung, liver and bone marrow.
The gold standard offers accurate diagnosis. The disadvantage is that it takes
6 weeks and is very expensive. For diagnosing active TB
