Lecture 11 The Mycobacteria Flashcards
Lecture
Objectives
The Mycobacteria
Background
a specific stain is used on mycobacteria because gram stain does not work very well on mycobacteria
Mycobacteria cell wall
Ziehl-Neelson stain
a red carbol fuchsin stain is added to the bacteria and is then washed out
the slide is decolourised with acidified alcohol
only bacteria that have the complex lipid mycolic acid are capable of retaining the stain
- mycobacteria have a very waxy cell wall that contains in it mycolic acid, that means they will remain stained red
-corynebacteria have this too but their disease manifests differently so you are not likely to confuse them.
this is the most important test for mycobacteria
Grouping Mycobacteria
all the major pathogens such as mycobacteria tuberculosis are small growers which makes it very difficult to diagnose
mycobacteria bovis are closely related to mycobacteria tuberculosis,
Mycobacteria bovis is a massive zoonotic risk to use from cattle and other animals and can cause the same disease in humans
M.ulcerans causes buruli ulcers, it causes a creeping necrosis of tissue and anaesthesia, so causes a painless ulcer
Tuberculosis
biggest killer of all infectious diseases
infects around 2 billion people a quarter of the worlds population but majority of people have an asymptomatic latent infection but these people could get an active disease later in life
Tuberculosis - a disease of poverty
Clinical Manifestations of TB
causes fever weight loss, 85% of TB is pulmonary, coughing transmits the bacteria to other people and people with the disease tend to lose a lot of weight
can cause disseminated TB is a common cause of disseminated meningitis (so the disease spread through the system and causes meningitis), the most common manifestation in children is disseminated TB (systematic spread through the blood stream)
The outcome of TB infection
the most common response is that our bodies can control the infection and bacteria will be latent
Transmission, protection and Pathogenesis of TB -1
is an intracellular pathogen
it is able to replicate in the macrophage
as it is resistant to being destroyed by macrophages, as it replicates in the macrophage it causes inflammation which attracts more immune cells and TB will escape its first cell and infect more macrophages and neutrophils and you eventually get a ball of immune cells and replicating TB, this ball is called a granuloma
the granuloma has in the middle a necrotic centre of dead immune cells, lots of immune cells on the outside and TB bacilli in the middle, this is called the granulomatous response which is protective and stops the infection going any further, this is probably where the latent infection in the lung sits or another probably sits in the draining lymph nodes, these are completely dependent on the immune system remaining competent
Transmission, protection and Pathogenesis of TB - 2
granulomas can be seen in Xrays, that TB can be contained for decades
Transmission, protection and Pathogenesis of TB - 3
in some people the granuloma is not good at containing TB, so TB encourages inflammation of the granuloma so that you get enough inflammatory damage around it that it eventually breaks into the airway of the lung and the centre of the granuloma (a caseous granuloma) is spewed into the airway of the lung and the person coughs up the bacteria and transmits it to others
so the pathology and transmission of TB is related to an immune response, the bacteria requires an immune response of transmission
the clinical syndrome requires an immune response means that the bacteria requires an immune response for its spread, the bacteria uses the immune response to both cause damage and spread, no toxins are involved, the immune response to the bacteria is what harms the person but the immune response if it gets it right is also able to contain the bacteria
CT axial-lung window of TB infected person
in someone with bad TB, in the lungs you have big air spaces where the walls between the alveoli have broken down due to the immuno pathology resulting in one big air space instead of lots of little alveoli for a big surface of gaseous exchange
image in the question shows a lung with lots of inflammatory damage and scar tissue and immune cells so you’ve no air spaces there and lungs are destroyed
Diagnosis of TB
if youve got a chronic cough, are losing weight and have night sweats and you go doctor and they send you for an x-ray and they will also take a sputum sample (Mucus and other matter brought up from the lungs by coughing.) they will look for the presence of bacteria in your sputum but not all people will be sputum positive
culturing the bacteria can take very long so can pose a problem so PCR can be used to detect the presence of mycobacterial DNA and some immunological tests that are also very fast and look for your immune response to the bacterium
TB control - strategies
Preventive vaccination
▪ Immunize prior to exposure with goal to
▪ Prevent establishment of infection
▪ Prevent infection from developing to disease
Antibiotic treatment
▪ Can target active TB or latent infection
▪ WHO has targeted active infection (transmission)
▪ Problem: Can’t treat 2 billion people with asymptomatic infection
TB can be eradicated if all people with active TB were treated and vaccinated
TB BCG Vaccine
it is a live vaccine
protects children from disseminated disease but less effective for adults so its effectiveness is dubious we probably need a better vaccine
TB treatment regimen
we give 4 drugs because most bacteria are killed initially but there are lots of persister cells (Persister cells are a small group of bacterial cells that can survive high levels of antibiotics and other antimicrobials)
the cells can be anywhere in the body, perhaps in a granuloma but they are not growing very much which makes them hard to kill
however because the antibiotics are being used for so long it means there’s a long time in which the bacteria have the opportunity to gain mutations and develop resistance to the antibiotics
the four antibiotics are given to reduce the chance of bacteria resistant to one antibiotic from becoming prevalent and spreading and hopefully the other antibiotics will take out the bacteria that gain resistance to one antibiotic
it can take 1000 antibiotics to complete the full treatment and some people will not want to persist once they feel as if they’re better
AMR and tuberculosis
multiple drug resistance bacteria
up to 18% of TB cases are multiple drug-resistant
MDR (multiple drug resistant)
XDR (extensively drug resistant)
Treatment regimen for MDR TB
Leprosy
was believed that we would have fully eradicated it
does not like growing in high temperatures
in humans it only likes growing in the skin and nasal passages because it does not like growing at 37 degrees celsius
hard to study as you cannot grow it on a petri dish
leprosy still exists in the UK in red squirrel populations only
leprosy disease
is an intracellular bacteria that can replicate in macrophages and even schwann cells that create a protective sheath around nerve fibers
- because they grow on schwann cells they can cause a lot of pathology and inflammation which results in nerve damage, the nerve damage can lead to paralysis and anaesthesia
- disease is caused by the inflammatory response to bacteria not by a toxin produced by the bacteria
Control of Leprosy
BCG is the vaccine designed to treat TB but is also very good at protecting against leprosy treatment may be required for months
