Introduction & Epidemiology

 

Tuberculosis (TB) is the 8th most common cause of death worldwide, accounting for 1.34 million deaths per year. One third of the global population are thought to carry latent TB and the majority of cases occur in the developing world. The UK incidence of TB is 12/100,000. TB is considered to be a re-emerging disease and immigration (from high prevalence areas), HIV (particularly in Africa) and emerging drug resistance are thought to be contributing to this. Figure 1 lists risk factors for contracting TB.

 

Microbiology

 

The bacteria Mycobacterium tuberculosis is the causative agent of TB. Figure 2 summarises the important microbiology of this organism. Infection is acquired by inhalation of aerosolised droplet nuclei from the airways of individuals with active TB. Coughing facilitates spread in this way.

 

Clinical Features of Pulmonary TB

Pulmonary TB is the most common disease resulting from TB infection and Figure 3 summarises the clinical features.

 

Investigations

 

Diagnosis of pulmonary TB is based on the clinical features of the patient, radiology (PA chest X-ray) and identification of AFB (acid-fast bacilli). The current gold standard in diagnosing TB is culture of the organism but this is a slow process, taking 6-8 weeks. Figure 4 summarises relevant investigations. Treatment should be started prior to obtaining culture results if the clinical picture is consistent with TB.

 

Treatment

 

  • Active pulmonary TB: See table below. A two month intensive phase of all four agents is followed by a 4 month continuation phase of rifampicin & isoniazid alone.

 

  • Active TB meningitis / miliary TB / tuberculous pericarditis: As for active pulmonary TB, except a 10 month continuation phase of rifampicin & isoniazid plus 2-3 months of oral prednisolone (double the dose if co-prescribed with rifampicin).

 

  • Direct observed therapy (DOT) should be used in cases where there are concerns over adherence to treatment. E.g. homeless, history of poor adherence.

Drug Resistance

 

Drug resistance is an increasing problem in managing TB. Incomplete courses of anti-tuberculous drugs are the main driving factor in the development of resistance.

  • Multi drug resistant TB (MDRTB) is resistant to at least isoniazid and rifampicin, accounting for 1% of TB cases in the UK. It should be suspected if a patient is culture positive after 2 months of treatment, has been in contact with a known case of MDRTB or has a history of previous anti-tuberculous therapy. Treatment should last 18 months and patients should be treated in isolation.

 

  • Extensively drug resistant TB (XDRTB) has been described in Asia, Americas & Europe, often associated with HIV co-infection. It is defined as resistance to isoniazid, rifampicin, a quinolone antibiotic and one other 2nd line agent. 

 

Prevention

  • Immunization: The BCG (Bacilli Calmette-Guerin) vaccine is a live attenuated vaccine, derived from Mycobacterium bovis. It is indicated for infants at increased risk of TB. Whilst it does not prevent infection, it reduces the risk of severe disease in childhood. As it is a live vaccine, it is contraindicated in HIV positive individuals.

 

  • Chemoprophylaxis: A 6 month course of isoniazid is indicated for contacts of active TB cases.

 

Extrapulmonary Manifestations of TB

 

Extra-pulmonary TB is the consequence of haematogenous spread of the bacteria and can result in two scenarios:

1. Miliary TB: bacteria seed the lungs and many other sites with multiple small foci of infection (1-5mm caseating lesions). Liver, bone marrow, spleen, adrenal glands, meninges and kidneys can all be seeded

 

2. Extra-pulmonary TB: non-miliary disease outwith the lungs. More common in HIV positive individuals.

  • Lymph nodes (most common site): usually cervical – “scrofula”
  • CNS: tuberculous meningitis; tuberculoma (brain parenchymal mass)
  • Kidneys: renal TB
  • Genitourinary: Genitourinary tract TB
  • Bones: osteomyelitis, tuberculous arthritis (destructive monoarthritis), Pott’s disease (infection in vertebrae).
  • Abdomen: intestinal (Crohn’s disease is main differential diagnosis) or peritoneal TB.
  • Pericardium: constrictive pericarditis and/or pericardial effusion

 

Other Important Mycobacteria

 

Mycobacterium tuberculosis complex:

  • M. tuberculosis
  • M. bovis causes TB in cattle. Transmission to humans is through drinking non-sterilized milk but pasteurization has made this a negligible risk.
  • M. africanum found in West Africa, causes TB in humans.
  • M. canetti is limited to the horn of Africa, less than 60 isolates ever reported. Causes TB in humans.

 

Non-tuberculous Mycobacteria (NTM):

Mycobacterium avium-intracellularecomplex (MAC) infection is uncommon except in AIDS, where disseminated MAC infection (commonly involving lungs & GI system) is often a terminal event.

 

Further Reading

 

Oxford Handbook of Infectious Diseases and Microbiology (1st ed., 2009, Torok E, Moran E, Cooke F). p.407-414

Mim’s Medical Microbiology (4th ed., 2008, Goering RV, Dockrell HM, Wakelin D, Zuckerman M, Chiodini PL, Roitt IM, Mims C). p.245-248

Davidson’s Principles and Practice of Medicine (20th ed., 2006, Boon NA, Colledge NR, Walker BR, Hunter JAA). p.695-703.

Robbins and Cotran Pathologic Basis of Disease (7th ed., 2005, Kumar, Abbas, Fausto). p381-388.

World Health Organisation: Tuberculosis

http://www.who.int/topics/tuberculosis/en/

National Institute for Health & Clinical Excellence: Tuberculosis Guidelines

http://guidance.nice.org.uk/CG117

 

For more in depth discussion:

Barry CE 3rd, Boshoff HI, Dartois V, Dick T, Ehrt S, Flynn J, Schnappinger D, Wilkinson RJ & Young D. The spectrum of latent tuberculosis: rethinking the biology and intervention strategies. Nature Reviews Microbiology 2009; 8: 45-55.

Giri PK. How could we have better vaccines against tuberculosis? Expert opinion in biological therapy 2008; 8: 1759-1772.

 

Image references:

  1. http://commons.wikimedia.org/wiki/File:Mycobacterium_tuberculosis.jpg
  2. http://en.wikipedia.org/wiki/File:Lungs_diagram_simple.svg

 

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