Friday 2 May 2014

Tuberculosis

Tuberculosis (TB)

Tuberculosis can take many forms. The most common found to infect humans is Myobacterium tuberculosis. Other forms include:

  • Myco canetti - a rare variant
  • Myco bovis - affecting mainly cattle and other mammals
  • Myco microti - mainly found to affect small mammals, such as voles 
  • Myco africanum - this type is considered to be between the human and bovine types, this type is mainly found within equatorial Africa.

Mycobacterium tuberculosis
This type is an acid alcohol fast bacilli, which is a term used to refer to the bacteria being rod shaped, and any gram stain cannot be washed away, even when treated with acid or alcohol. Stains used are Ziehl-Neelson stains (red, slightly curled appearance, beaded, almost looks as if they're branched) or Auramine Phenol stains, this is because these stains can infiltrate the mycolic acids (consisting of 60-90 waxy carbon compounds, these are a protective layer) located within the cell walls of the bacterium, whereas gram stain cannot.

MTB is an obligate aerobe, thus require the presence of oxygen in order to grow. They are non-motile are do not create spores. They are also not contained within capsules. They cordate in broth culture, this is where they form the shape of a heart? They grow slowly due to the presence of their complex mycolic acid wall. 

Can be grown on a Lowenstein-Jensen medium, which is egg/glycerol based. It can go within 2 weeks of a subculture, but it can take up to 8 weeks on a primary isolation. During this time the sample can be contaminated, if this occurs, in order to decontaminate sodium hydroxide is used, and then it is neutralised.

MGIT and BacT Alert systems can be used, these are a continuous monitoring liquid culture. 

For diagnosis, nucleic acid probes can be used with the use of PCR. This is rapid and reliable, and can be used to detect resistance. 
The T-SPOT test can be used to look for activated T cells. Useful for when TB is latent and also in outbreaks. The organism can come out of latency if the patient is given a high dose of steroids.
Interferon gamma test and tuberculin skin tests can also be used. 

Treatment
Antibiotics can be used to treat this bacterium, however many can struggle to penetrate the waxy layer. Ones that are generally used are Rifampicin, Ethambutol and Isoniazid, these are 1st line antibiotics. Multiple treatments may be used in order to prevent any resistance, as this can cause treatment failure. Multiple drug resistance tuberculosis - when resistant to 1st line antibiotics. 

Primary tuberculosis
This is usually contracting from inhalation of TB droplets in the air. The organism is then engulfed by the alveolar macrophages, where they then replicate in order to form the initial lesion. This is then carried by the phagocytes to the lymph nodes. This can then further spread to other organs and other parts of the lungs. In 90-95% of infected individuals, haematogenous spread occurs. The DNA of the bacterium can be detected in tissues by in situ PCR. In 5-10% of infected individuals TB will progress to cavitary TB, this is where the cavities open into the bronchi allowing spread of TB through coughing. 

Myco bovis can be contracted through the ingestion of milk. It affects the tonsils, lymph nodes and the intestines. It can be spread by macrophages to the local lymph nodes through the bloodstream. It can also reach other organs such as the spleen, kidneys, CNS and bone marrow. It can become dormant and resurface years later.

Clinical disease
5% of patients exposed to the active disease show it developing in 2 years. 5-10% later in life. Those who are HIV positive, 10% show the active disease within 1 year. It's more likely to spread to extrapulmonary sites, which can progress quickly to death.

Pulmonary TB is present in 80% of cases, and extrapulmonary in 20%.
Extrapulmonary cases are made of:
  • Meningitis
  • Lymphatics
  • Pleural
  • Genito-urinary
  • Bone/joint
  • Others
Symptoms of the disease are malaise, weight loss, coughing, night sweats and haemoptysis.   

The organisms can be protected within necrotic or caseous granulomas. These can become calcified. This is referred to as cavitating disease, this can cause tissue destruction. This infection can be lifelong. 

Central nervous system infection
TB infecting the CNS, this can cause meningitis. Meningitis has an insidious onset, can cause confusion and headaches, it is an acute rapid disease. It results in a raised lymphocyte count, and is very difficult to diagnose as there can be very low amounts. Will cause an altered mental state. 

Miliary TB
This is a disseminated primary disease, it is named due to the many "millet seed" sized lesions on chest X-ray, which look like bird seed. Patients can also have meningitis and a sepctic of typhoidal presentation.


In accordance to the WHO, it was confirmed a few years ago that the emergence of extensively drug-resistance tb (XDR-TB resistant to 2nd line drugs) poses a serious threat to public health, particularly when associated with HIV.