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
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.
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.
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.
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.
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
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
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.
Tuberculosis
Tags: bcg, izoniazid, miliary, rifamipicin, tb
Hotton, P. Tuberculosis, Don't Forget the Bubbles, 2014. Available at:
http://doi.org/10.31440/DFTB.5410
Tuberculosis is the second greatest killer worldwide due to a single infectious agent and is a massive public health concern.
What causes it?
It is caused by 5 closely-related Mycobacteria
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:
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?
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
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:
What is the treatment?
TB is a treatable and curable disease
DOTS and the Stop TB Strategy recommended by WHO
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
References
About Paul Hotton