Tuberculosis Flashcards
What are the main symptoms of tuberculosis?
Fever, Night sweats, persistent coughs, bloody phlegm, chest pain/shortness of breath
Fever and Night sweats are more specific to TB compared to other colds
Describe the immune response to TB exposure
TB has a long asymptomatic period - patients can be infected years before symptoms and then have a quick symptom onset
exposure: 4-6 weeks when dendritic cells interact causing an adaptive and innate immune response. macrophages take up TB trying to kill it off causing more and more macrophages and dendtrictic cells coming together- forms a granuloma in an attempt to contain TB which can lead to more infectious issues. The macrophages can destroy TB- becomes latent TB (asymptomatic) which never becomes active TB.
What are the 4 stages of TB?
Primary infection
Latent period
active TB - have symptomatic TB
Transmission - primarily by patients with active TB.
Describe the difficulties in diagnosing TB
difficult to diagnose: occurs mostly in resource limited settings.
molecular testing and whole genome sequencing used - difficult when there are millions of cases in a country every year. can be expensive.
Diagnosis of TB
Different tests preferred at different suspected stages of TB
Tuberculin skin test used to look for latent TB - antigen for TB injected under the skin and left for a few days, if a bump appears the patient usually has latent TB.
microscopy - nelson stain used ( N/A for gram stain). TB bacteria stains red, but they cant always be seen - high sensitivity but low specificity.
X-ray
CT Scans if TB is extra-pulmonary (outside of the lungs)
culture growth - TB bacteria wont grow on most things in the lab/ grows very slowly so TB bacteria has specific culture conditions which can be solid/liquid.
Gene expert machine: Found in a clinical lab for diagnosis using a PCR approach. Probes detect a specific gene from the sample and show if that gene is present. Primary way for diagnosis using sputum from patient, very easy machine to use for people not highly trained in molecular biology
Describe Mycobacterium Tuberculosis
Rod shaped bacterium, waxy cell wall, strict anerobe , genome of 4.4/4.5 mega bases in size, one single chromosome, no plasmids
Historical epidemiology of M.TB
started in africa about 73,000 yearsa go and spread as humans spread around the world
Modern epidemiology
9 lineages of TB that infect humans occurring in different parts of the world. Lineage 4 occurs in every country that has TB
lineage 2 also very prevalent, primarily in Asia but also in Europe too. Other lineages have a more restricted distribution geographically.
Also different in terms of their virulence/pathogenicity but primarily act in a similar way to each other.
Tuberculosis Incidence and Epidemiology
Poverty related disease- occurs primarily in poverty related and resource limited countries - in low poverty areas people generally have lower health and worse immune systems, live more closely together, share beds ect.
Incidence comparisons should be per 100,000- larger countries can have many infections but a lower incidence.
high surveillance results in more active cases being reported, but doesnt mean that there are actually more cases occuring - look at the number of tests taken and how many were positive
Countries with low indicence can have pockets of high incidence - TB is poverty related.
Treating TB
difficult to treat
takes a long time to treat
patient dependent - patients can be treated with more drugs if they are sensitive to them
first line of drugs: a combination of ioniazad/ rifampicin drugs. Isoniazid, Ethambuotal, Moxifloxacin, Rifamipicin, Rifapentine, pyrazinamide
second line of drugs: more side effects. floroquionolones.
TB first line of treatment
patients sensitive to all drugs take a minimum of 4 months to treat, normally 6
normally 2-3 pills every day for normally 4 months at least,
resistance-> second line drugs are used which are normally up to 99 months worth of treatment
adhernace to taking these drugs and effectiveness of these drugs over such a long period of time can be a challenge.
minimal side effects, main side affects are ioniazid turns urine bright orange
typical first line treatment for TB
isoniazid and rifampicin are the backbone.
Normally two months of isoniazid, rifampicin, pyrazinamide and ethambutol followed by four months of just isoniazid and rifampicin.
W.H.O: two months of all four tablets followed by two of just isoniazid and rifampicin.
moxifloxacin used if issues are encountered with these drugs or the patient cant use one of these drugs
resistance to primary isoniazid/ rifampicin: second line of treatment must be used.
Second line of treatment
Consists of core drugs which do most of the killing, support drugs to reduce resistance
also dependent on which drugs have the least amount of side effects for the patient. Side effects include deafness/ psychotic episodes - balance between treatment and life changing side effects. As many group A drugs should be taken as possible (highly effective, well-tolerated, generally fewer side effects). Group B taken with constant monitoring, and group c added based on drug resistance patterns and side effects. Minimum of 9 months of treatment - symptoms go away within about a week
Issues with second line of treatment
patient adherence to drug treatment stops after a week: dormant TB reactivates once drug pressure goes away causing a secondary infection and secondary reactivation typically with drug resistance.
Drug Resistance Mechanisms
Intrinsic methods: Impermeable cell wall, efflux pumps, enzymes
acquisition via mutations in genes: no plasmid. No horizontal gene transfer, all resistance for TB drugs occur from mutations in the targets of those drugs.
