Tuberculosis and drug resistant TB: A global health prospective Flashcards
What is TB?
TB is the 13th leading cause of death worldwide
since 2007 - leading cause of death from a single infectious agent
(before COVID-19)
ranking above HIV/AIDS and malaria
WHO declared TB a global health emergency in 2003
Define TB and the causal agent
a contagious, debilitating (consuming) bacterial disease
spread by airborne droplets from an infected person
Caused by a bacterium
(Mycobacterium tuberculosis)
slow growing, difficult to kill due to its
Lipid rich waxy outer cell wall coat
- Hard to treat by standard antibiotics
- coughing speaking sneezing, you can infect someone with TB
- Generation time of 24hrs
Left untreated, one person with tuberculosis
will infect 10-15 people (R0). Governments try to keep R under 1
R value of TB is between 15 and 20
Controversial because it takes years to find out whether someone has the disease or not
Describe the infectious dose, incubation and Colonization
Mycobacterium tuberculosis has an incredibly low infectious dose of less than 10 microorganisms.
These bacteria have a long incubation period of two to twelve weeks with a range from 2 weeks to decades
This bacteria, having the ability to be latent or cause disease, is what causes this range.
Mycobacterium tuberculosis that infects the lungs is inhaled by the host and engulfed by the macrophages of the alveoli.
These bacteria can now lay dormant or begin to reproduce inside the macrophages, which triggers the infection to occur.
What are the percentages of pulmonary and extrapulmonary TB?
- M.tuberculosis can infect many parts of the body
- 85% pulmonary TB
- 15% extra-pulmonary TB
- Like interstitial fluid
In HIV infected patients, only 30% of cases are pulmonary TB.
If someone is HIV ++, then they have a higher rate of non pulmonary TB
Where are the places that TB could infect?
Spread of infection by haematogenous spread (spread
Via blood)
Pleural disease
Lymph nodes – scrofula
Pericardial
Skeletal –Potts disease
Genitourinary
Gut
Peritoneal
Miliary
Meningeal
What are the characteristics of a pulmonary TB infection on an x-ray?
Multiple cavities
Circular holes-> due to necrotic tissue caused by bacteria
Thickening of lymph nodes
TB maybe located in one particular section, instead of multiple
What is miliary TB?
Miliary tuberculosis is a potentially fatal form of the disseminated disease due to the hematogenous spread of tubercle bacilli to the lungs, and other organs. It results in the formation of millet seed-sized (1 to 2 mm) tuberculous foci.
Comes up differently under chest xray
Normal TB= encapsulated]
Milliary= disseminated
Acute miliary TB is seen under 40 years of age. Most of the patients present with constitutional symptoms or can have signs and symptoms related to one organ owing to the systemic nature of the disease. Evening rise of temperature and night sweats of 1-2 weeks duration are classically described, although a patient can have early morning fever spikes.
What is Potts Disease?
Pott disease, also known as tuberculous spondylitis, is a classic presentation of extrapulmonary tuberculosis (TB).
It is associated with significant morbidity and can lead to severe functional impairment
Pott disease, or tuberculosis of the spine, has recently shown a significant resurgence in developed nations secondary to global migration. Concurrent with this phenomenon, multidrug-resistant bacterial strains of tuberculosis have been increasing in developing nations over the past decades.
What is a Scrofula?
Scrofula is a condition in which the bacteria that causes tuberculosis causes symptoms outside the lungs.
This usually takes the form of inflamed and irritated lymph nodes in the neck.
Doctors also call scrofula “cervical tuberculous lymphadenitis”: Cervical refers to the neck.
Describe the mechanism of m.tuberculosis,
including
exposure, to latency, to reactivation to active disease
About 30% of people are infected in the presence of TB aerosol
Of that 30%, only 5% go on to progress to active TB Everyone else goes into latency (no disease but they areTB infected)
Of these latent infections, you can diagnose via Mantoux test(hyperactivity of TB antigens) or blood test
Positive test= hypersensitivity to TB antigens
If you have latent Tb, you have a 10% lifetime risk of reactivation to active TB
Always a reservoir of infection
We don’t know is whether latent TB is driven by immunological protection
However immunosuppression increases the chances of reactivation to activation of TB by 5% by year
The spread of TB is mainly driven by pulmonary Tb
It is very difficult to spread spinal TB
What is latent TB?
Latent tuberculosis infection (LTBI) is defined as a state of persistent immune response to stimulation by
Mycobacterium tuberculosis antigens without evidence of clinically manifested active tuberculosis (TB) disease. Individuals with LTBI represent a reservoir for active TB cases
How many people are infected with latent TB?
1/3 world’s population infected
BCG TB vaccine is largely ineffective for adult pulmonary disease
Preventive drug treatment possible but not practical
Antibiotics don’t work on latent TB
Not wise to provide antibiotics to the world due to Antibiotic resistance, Cost production and possible
Reactivation many years later
What are risk factors for reactivation of latent TB?
- reactivation occurring only when the immunity of the host is compromised.
- Malnutrition
- Poverty
- Immunosuppression
- Old age
- People become
partially
immunosupressed - Poor health
- HIV
Poverty, immunosuppression and malnutrition are liked with TB
What is the diagnosis of Pulmonary TB?
Blood:
Interferon (IFN)-gamma blood test.
- T-cell response to Mtb proteins
Interferon-γ release assays (IGRAs) depend on this immune reaction involving T helper cells to detect latent TB through quantification. Fresh blood samples are mixed with antigens and controls to test to determine if an individual has indeed contracted an infection.
Mantoux test
Chest X-ray: CT scanning
Sputum/ culture
GeneXpert–PCR
Bronchoscopy
Biopsy
How to significance of diagnosing TB via sputum?
Sputum: Cough or induced
- Smear/ culture
Sputum smear microscopy remains the most common way to diagnose pulmonary TB. Depending on the report and method used, smear microscopy can accurately detect TB in 20% to 80% (using fluorescence microscopy methods) of TB cases.
Limitations:
can only be used to diagnose TB when sputum has sufficient bacillary load, and it cannot detect drug resistance.
Thus, HIV-associated TB often goes undetected because people living with HIV (PLHIV), especially those with severe immunosuppression, generally have very low numbers of bacilli.
What is the significance of GeneXpert?
- Xpert is more sensitive than sputum smear microscopy in detecting TB, and it has similar accuracy as culture.5-6
- Moreover, its ability to detect smear-negative TB provides a significant advantage, especially for PLHIV.
- , its ability to detect RIF-resistant TB in less than 2 hours significantly improves the likelihood of timely treatment initiation. (Conventional culture and drug-susceptibility testing [DST] are still required to complete the drug-resistance profile and to monitor treatment.)
Limitations of GeneXpert?
Xpert does cost more than smear microscopy; it requires a machine that currently costs US$17,000 and cartridges that cost US$9.98 for each test, in addition to human resource and other running costs.
It also has operational limitations, such as the need for a sustained power supply.
However, Xpert is intended to be used at facilities close to the patient to reduce the time to diagnosis and TB treatment initiation.
What is the Mantoux test? What are the principles of the The Mantoux tuberculin skin test (TST) ?
The Mantoux tuberculin skin test (TST) is one method of determining whether a person is infected with Mycobacterium tuberculosis. Reliable administration and reading of the TST requires standardization of procedures, training, supervision, and practice.
Inject with PPD (or purified protein derivative)
Strong response= more likely that you are progressing towards more active disease
More antigen around
However, reactivity does not mean disease. It just means exposure.
What are the principles of the Mantoux test?
The reaction to intracutaneously injected tuberculin is the classic example of a delayed (cellular) hypersensitivity reaction.
T-cells sensitized by prior infection are recruited to the skin site where they release lymphokines.
These lymphokines induce induration through local vasodilatation, oedema, fibrin deposition, and recruitment of other inflammatory cells to the area.
Features of the reaction include (1) its delayed course, reaching a peak more than 24 h after injection of the antigen; (2) its indurated character; and (3) its occasional vesiculation and necrosis.
What is the BCG Vaccine?
This is an attenuated vaccine
Attenuated M.bovis Bacillus Calmette-Guerin
The most Heavily used vaccine in medical history
Until the COVID vacciens
Given Usually to infants or in early childhood
Protects against disseminated primary infection
Ineffective against reactivation adult TB
Poor data to show that BCG shows any effect on adults
Describe the graph showing TB prevention in terms of the USAGE of the BCG vaccine.
In North America (Particularly in USA & Canada) AND Italy, the BCG vaccine is used for specific groups
For most of the old world (barring western europe), South America (barring Ecuador), Microasia, Greenland and Mexico, the BCG is a vaccination that is utilised for all.
For Western Europe (like the UK, France, Spain,) and Oceania (Australia, New Zealand) etc… the BCG vaccine used to be used for ALL children.
What is the global plan to end TB (between 2016 and 2020)?
Reach at least 90% of all people with TB and place them in appropriate therpy first-time, second time and preventative therapy as required
Reach at least 90% of the key populationd most vulnerable and at risk.
Achieve at least 90% treatment success for all people diagnosed with TB through affordable treatment services, adherance to complete and correct treatment, and social support.
What are the 2020 targets for the reduction of TB incidence rate and TB deaths and the catestrophic costs?
*
What is the missing 4 million?
“four million people are “missing” and are either not diagnosed or treated or receive care that is of poor quality”
No high burden country achieved both treatment coverage and success
Greatest gap - in treatment coverage
