Tuberculosis Flashcards
What are the ‘three big killers’?
HIV
Malaria
TB
What is TB strongly associated with?
HIV
How many deaths happen per year due to TB?
1.4 million
How many new cases of TB arise per year?
8.7 million
What percentage of cases of TB happen in Africa?
90%
What percentage of HIV patients have TB?
13%
What fraction of TB deaths are associated with HIV?
2/3
What type of people normally suffer from TB?
Vulnerable population
Homeless, refugees
No access to appropriate health care
How can TB rates be used to assess a country?
TB rates can be used as a marker to determine the effectiveness of the health care system in a country
Why were TB rates so high 100 years ago?
Many reasons
One were the tight living quarters in households
Allowed airborne disease to spread easier from one individual to the next
What caused the spike of TB in the 80s?
AIDS
Why are HIV and TB so closely related?
Both affect the same cells
What has happened to the rates of TB?
Decreased
But TB has become more of a global problem due to the globalization of the world and increased population in cities
What is the TB capital of Europe?
London
What has caused London to be the TB capital of Europe?
Immigrant population that has settled in the city
What are strains of TB specific to?
Populations
Current treatments are adequate at tackling the TB epidemic
TRUE or FALSE
FALSE
Though effective, these drugs are inadequate at tackling the global TB epidemic
What are the problems of current therapies for TB?
Need to take the drugs for a long time
The therapies are too complex, since it requires a combination of drugs
TB drugs interact with HIV drugs
Examples of drugs used in TB
Rifampicin
Isoniazid
Streptomycin
Ethambutol
What strategies have been developed to tackle the complications of current drug treatments?
DOTS involves making the patients film themselves, attend a clinic or be supervised by a friend whilst taking a drug to make sure the patient is undergoin therapy
Current TB therapies are the same as in the 60s
TRUE or FALSE
TRUE
Why are some TB therapies not effective?
TB expresses epitopes shared with other mycobacteria
Many people have been expressed to these epitopes, they will have garnered resistance to these trains
What is wrong with the current drug development system?
Not effective at propagating the discovery of new drugs
Long process that takes lots of phases of development
What are the two types of resistant TB?
Multidrug resistant TB
Extensively resistant TB
What drugs must a TB strain be resistant to in order to be a MDRTB?
Resistant to Risampicin and Isoniazid
How many people develop MDRTB
500 000
What proportion of MDRTB sufferers are diagnosed?
1/4
How many cases of MDRTB are successfully treated?
1 in 9
What drugs must a TB strain be resistant to in order to be a extensively resistant TB strain?
Rifampicin
Isoniazid
Fluoriquinolone
At least one of the three injectable drugs
How does TB spread?
Aerosols
What does TB infection look like?
TB leads to lung infection
Resolution of the disease leads to local scarring due to the damage caused
Miliary spread
Can either lead to local infection or spontaneous resolution
Why are immunocopromised patients more at risk of TB infection?
T cells protect the host from the dissemination of the disease
What is the risk of reactivation of TB?
10%
What are the big challenges in terms of the bacteria itself, that makes treating TB difficult?
Cell wall
Slow growth
Persistence to antibiotics
Granuloma
What about the cell wall of M. tuberculosis makes TB hard to treat?
TB is neither gram positive nor gram negative
Thick lipid bilayer prevents entry of the drug into the bacterium
What about the slow growth of M. tuberculosis makes TB hard to treat?
Difficult to model
Doubling time is 24 hours
What about the persistence of M. tuberculosis makes TB hard to treat?
It can spread to surrounding bacteria
How does the granuloma make TB harder to treat?
The core of necrotic tissue makes it difficult to target the bacteria since the host can’t recognise them
TB populations remain in the host even after effective drug treatment
TRUE or FALSE
TRUE
What hypotheses have been developed to explain why TB populations stay in the host following effective treatment?
Bacterial population changes and evolved to counteract the action of the drugs
There are two distinct populations of bacteria, one fast growing that is effectively targeted in the beginning, and a slower growing population that is resistant to the drugs and remains in the host at lower concentrations
What hypothesis regarding why TB remains in the body following effective treatment was right?
There are two distinct populations of M. tuberculosis
How does Rifampicin affect the TB population?
Acts on RNA polymerase
How does Isoniazid affect the TB population?
Acts on the cell wall turnover via fatty acid synthase
How does Ethambutol affect the TB population?
Acts on cell wall formation
How does Pyrazinamie affect the TB population?
Prodrug
Uknown population
What drugs are used as a first stage treatment of TB?
RIfampicin, Isoniazid and Ethambutol
Decrease the concentration of active mycobacteria
What was shown about fast and slow-growing mycobacteria in culture?
The fast-growing mycobacteria reacted more to Isoniazid than slow-growing
What was revealed about the gene expressions of fast and slow growing bacteria in TB?
They contained different gene expressions
What type of bacteria are Mycobacteria Tuberculosis according to the hypothesis that was proven?
M. Tuberculosis are fat and lazy
React indifferently to drugs
Enter a state of quiescence and reactivate when the host becomes immunocompromised
