Tuberculosis - cough

Tuberculosis

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Jamie is a 4 year old with ongoing pyrexia for a couple of weeks.  He has a mild cough but nothing else.  The family mention in passing that grandad recently had TB.

Is this common in the developed world?  How would you recognise it and treat it?

 

Tuberculosis is the second greatest killer worldwide due to a single infectious agent and is a massive public health concern.

Bottom Line

  • Tuberculosis is a global burden, although rare in developed countries
  • Children don’t always have the typical presentations of TB and are at greater risk of extra pulmonary disease
  • Small number have the classic triad for TB diagnosis
  • Tuberculin skin test >15 mm is diagnostic of TB but new tests (IGRA) more specific and sensitive
  • TB is treatable and curable
  • Treatment needs good directly observed therapy to reduce multi drug resistant TB

What causes it?

It is caused by 5 closely-related Mycobacteria

  • Mycobacterium Tuberculosis
  • M. Bovis
  • M.Aficanum
  • M.Microti¡
  • M. Canetti

Tubercile Bacilli are a non spore-forming, non motile, weak gram-positive curved rod.  Its hallmark is its acid fast capacity.

Each mycobacteria has its own unique fingerprint of mycolic acids.

It is slowing growing.

Isn't it just found in developing countries?

It is much more common in developing countries.  The reasons for this are: HIV epidemics; population migration; overcrowding/more populated countries; increased poverty; inadequate health coverage and poor access; and inefficient TB control programs.

How is it transmitted?

TB is trasmitted person to person – usually by air bourne mucous droplets .

Adult patients have copious production of sputum and a severe forceful cough and environmental conditions such as poor air circulation exaberates the risk.

However in children with TB, the cough is often absent and they lack tussive force required to suspend infectious particles of correct size.

What do all the TB terms mean?

Primary Pulmonary Disease

There is parenchymal/pulmonary foci in 70% of cases.  Initially the inflammation is not seen on CXR, but there is tissue hypersensitivity which leads to large regional lymph nodes.  This leads to lobar pneumonia and progressive primary pulmonary disease (rare).

 

Extrapulmonary Disease

There is where there is clinical TB outside the lungs – e.g. lymph nodes, pleura, brain, kidneys, or bones.

 

Disseminated TB

This is where there is spread to other organs due to primary TB.

 

Reactivation TB

Healed TB remains in the lung with no extrapulmonary spread.  Reactivation is rare in childhood – those <2 years of age rarely acquire  reactivation.  It is more common >7 years of age or in adolescents.

 

Miliary TB

This is where tubercles form in different organs due to dissemination of bacilli through the body by the blood stream/lymphatics.  It varies in severity.

What are the symptoms?

This depends on the age and type of TB and there are a wide spectrum of clinical presentations.

The majority of children with TB develop no signs or symptoms.  They can occasionally have low grade fever/mild cough and there is rarely the ‘classic’ of high fever, cough, night sweats, weight loss, lethargy.

Younger infants <2 years are more likely to have extra pulmonary TB

The mild symptoms can go on for many months resulting in delays in seeking care and increased transmission rates.  TB can infect up to 10-15 other people through close contact over the course of a year and this emphasises the importance of contact tracing.

So what are the most useful clinical indicators of TB?

A Melbourne review for ICHRC (2008) recommended:

Consider TB in…

Unexplained weight loss/failure to grow normally

Unexplained and prolonged fever >2 weeks

Chronic cough >30 days

Exposure to an adult with probable/definite TB

Where does transient microscopic haematuria come in?

Transient microscopic haematuria is a common sign of TB infection

Haematuria has been noted to be a presenting symptom of urinary tuberculosis.  Renal TB is rare and manifests in adulthood but can present in children.

There is thought to be an association between haematuria and mycobacterial infection (Dworkin et al).

Where can TB affect, other than the lungs?

TB can affects pretty much anywhere in the body: middle ear; tonsils; pericardium; CNS; bones; muscle; intestine; epididymis; liver; adrenal glands; kidneys.

How is it diagnosed?

  • CXR
  • Tuberculin skin test
  • History of exposure
  • Cultures should be obtained
  • Confirmation with: induced sputum – difficult in infants; gastric aspirates – 50% yield
  • Look for disseminated/extra pulmonary disease (these can predict/change length of treatment)

Check out how to perform the tuberculin skin test.  And how to read the results.

 

Causes of false positives for the tuberculin skin test (TST)

Cross sensitisation to antigen of non TB mycobacteria

Previous vaccination with BCG (especially if 2 X BCGs)

Boosting effect of multiple TST (increased reaction to TST with serial testing)

Half of infants who receive BCG vaccine never develop a reactive TST

Older children and adults do get tuberculin reactivity.  This is normally <10 mm.  If >10 mm then this warrants further investigation for TB.

 

Interferon gamma release assays

Two tests

  • T.spot TB
  • Quantiferon TB Gold

Detect interferon gamma generation by patients T cells in response to specific M. tuberculin antigen:

Disadvantage: cost and specialised equipment.

Advantage: one person encounter; lacks cross reaction with BCG and other mycobacteria; an absence of boosting.

 

A meta-analysis in 2008 (Pai et al) showed:

Specificity of 98% for the Quantiferon tests: 99% in patients not vaccinated with BCG, and 96% in BCG-vaccinated patients.

T-SPOT TB test appears to be more sensitive for latent tuberculosis than the Quantiferon tests or tuberculin skin testing.

What is the treatment?

TB is a treatable and curable disease

Standard. Primary TB ( UK – NICE Guidelines and WHO guidelines)

  • Six-month course of three antimicrobial drugs to reduce secondary drug resistance
  • Izoniazid(H), rifampin(R), pyrazinamide(Z)

If no CNS disease

  • HRZ for 2 months; Then HR for the remainder of 4 months (so total 6 months)

DOTS and the Stop TB Strategy recommended by WHO

  • Supportive care
  • Notifying public health

N.B. isoniazid resistance can happen – add fourth agent either streptomycin/ethambutol/ethionamide.  The reason for fourth is that pyrazinamide is not effective in preventing emergence of rifampin resistance.

 

Multi drug resistant TB

Standard anti-TB drugs have been used for decades, and resistance to the medicines is growing.

Multidrug-resistant tuberculosis (MDR-TB) is a form of TB caused by resistance to, at least, isoniazid and rifampicin

Inappropriate treatment, poor quality medication and poor adherence main cause of MDR- TB

Use second-line drugs (although it is rare in children)

If suspected Use 4 anti-TB agents till cultures – this requires longer treatment therapy 

What are the adverse effects of the medication?

Isoniazid

Antibacterial activity only against mycobacteria (first line)

Mild hepatic enzyme elevation, hepatitis, peripheral neuritis, hypersensitivity

 

Rifampin

Bactericidal activity – intracellular and against slow and intermittently growing bacteria

Orange discoloration of secretions or urine, staining of contact lenses, vomiting, hepatitis, influenza-like reaction, thrombocytopenia, pruritus

 

Pyrazinamide

Hepatotoxic effects, hyperuricemia, arthralgias, gastrointestinal tract upset

 

Pyridoxine

Vitamin B supplements given to combat izoniazid side effects 

How do we prevent it?

TB is prevented through: case finding and treating – 30-50% of household contacts to infectious case are TST +ve and 1% have overt disease; public health/chest clinics; BCG vaccination

 

BCG vaccination

  • Only vaccine available
  • Initially derived from M.bovis and given by intradermal injection
  • Dosing schedule varies (WHO – single dosing in infancy)
  • Optimal age unknown and some countries repeat the vaccine
  • Most reactions are mild and resolve
  • Immunocompromised patients have a higher risk of disseminated TB
  • BCG is 50% effective in preventing TB – higher in disseminated and meningeal TB

References

Marais BJ, Gie RP, Schaaf HS, Hesseling AC, Obihara CC, Starke JJ, Enarson DA, Donald PR, Beyers N. The natural history of disease of childhood intra-thoracic tuberculosis: a critical review of the prechemotherapyiterature. Int J Tuberc Lung Dis 2004;8:392-402.

Azzopardi P, Graham S. What are the most useful clinical indicators of tuberculosis in childhood? International Child Health Review Collaboration  2008.

Dworkin G, Reisman L, Ben-Zvi Z, Lieberman KV. Association of hematuria and mycobacterial infection. Child Nephrol Urol. 1991;11(1):44-6.

Pai M, Zwerling A, Menzies D. Systematic review: T-cell-based assays for the diagnosis of latent tuberculosis infection: an update. Ann Intern Med 2008; 149:177–184.

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