Jinja Regional Referral Hospital
Nalufenya Road
Jinja
Uganda
Management of Tuberculosis in Children
Title of Guideline (must include the word “Guideline” (not protocol, policy,
procedure etc)
Guideline for
Contact Name and Job Title (author)
Dr C Gilhooley
Dr J Morgan
Dr Namasopo
Directorate & Speciality
Paediatrics
Date of submission
Date on which guideline must be reviewed (this should be one to three
years)
Explicit definition of patient group to which it applies (e.g. inclusion and
exclusion criteria, diagnosis)
March 2013
March 2016
Abstract
This guideline describes the causes, assessment
and management of tuberculosis in children
Key Words
Fever, difficulty in breathing, shortness of breath,
pleural effusion, weight loss, cough
All children and young people
Statement of the evidence base of the guideline – has the guideline been
peer reviewed by colleagues?
Evidence base: (1-5)
1a
meta analysis of randomised controlled trials
1b
at least one randomised controlled trial
2a
at least one well-designed controlled study without randomisation
2b
at least one other type of well-designed quasi-experimental study
3
well –designed non-experimental descriptive studies (ie comparative /
correlation and case studies)
4
expert committee reports or opinions and / or clinical experiences of
respected authorities
5
recommended best practise based on the clinical experience of the
guideline developer
Consultation Process
Paediatric Clinical Staff
Target audience
All paediatric staff involved in treating malaria
Clinical guidelines are guidelines only. The interpretation and application of clinical guidelines will remain the
responsibility of the individual clinician. If in doubt contact a senior colleague or expert. Caution is advised
when using guidelines after the review date.
Gilhooley
Page 1 of 10
March 2013
Jinja Regional Referral Hospital
Nalufenya Road
Jinja
Uganda
Management of Tuberculosis
Summary
This guideline reviews the burden of disease of Tuberculosis (TB) in Uganda and the need for clear
diagnosis and management. It also reviews the common organisms causing TB and the different treatment
options available. The guideline also aims to look at follow-up of patient to ensure compliance with
medication and how to improve compliance. Finally there is a review of contract tracing and its importance
in TB.
Gilhooley
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March 2013
Jinja Regional Referral Hospital
Nalufenya Road
Jinja
Uganda
Acute Treatment algorithm for Tuberculosis
Yes
History
Cough > 2/52 +/- wheeze
Not growing/weight loss
Fever >2/52
Exposure to infectious TB
Night Sweats
No
Examination
Pleural effusion
Enlarged tender LN, especially in neck.
Signs of meningitis
- Especially if developed over
days
Abdominal swelling
Joint/bone/spine swelling or deformity
Yes
No
Unlikely TB consider alternative diagnosis
Treatment for
pneumonia/worms/diarrhoea/bacterial
meningitis failed. Reconsider diagnosis of
TB
Airway
- ensure if safe.
Breathing
- Cyanosis – give oxygen
- Respiratory distress (indrawing, RR)
Circulation
- Weak pulse/CRT>3 seconds – consider
10mls/kg fluid bolus
- Ensure drinking/BF – if not consider NGT or IV
fluids
Disability – AVPU and glucose
- If AVPU = V,P,U consider TB meningitis and
need for LP
- Monitor for raised ICP – pupils, eye deviation
- If glucose <2.2 give bolus 10% glucose
- LP if no contraindications.
Exposure
- Check skin, bones, joints, spine
- HIV positive?
Investigations
- AFBs – gastric/CSF/pleural/ascetic
- CXR
- PPD skin test
- HIV test
Counselling of child and carers
Treatment
Smear -ve PTB/Non-severe EPTB
2HRZ + 4HR (+ 6 months pyridoxine)
Smear +ve PTB/Severe EPTB/Severe concomitant HIV infection/smear –ve PTB +severe
parenchymal disease
2RHZE + 4HR (+ 6 months pyridoxine)
TB meningitis + TB arthritis
2RHZS + 4RH (+ 6 months pyridoxine)
Prednisolone 1mg/kg OD for 1 month
Previously treated smear +ve PTB
2HRZES/1HRZE + 5HRE
Chronic and MDR TB
Specialised regimes – discuss with expert.
H = Isoniazid, R = Rifampicin, Z – Pyrazinamide
E = Ethambutol S = Streptomycin.
Doses on page 7.
Gilhooley
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If on ARVs consider interactions and adjust
medications or doses appropriately. If
unsure discuss with colleague.
March 2013
Jinja Regional Referral Hospital
Nalufenya Road
Jinja
Uganda
Introduction
Uganda ranks 16th on the list of 22 high-burden tuberculosis (TB) countries in the world. In 2007, the country had
almost 102,000 new TB cases, with an estimated incidence rate of 330 cases per 100,000 population. i
Causes of Tuberculosis
Tuberculosis is common, and in many cases lethal, infectious disease caused by various strains of mycobacteria,
usually Mycobacterium tuberculosis,ii a small, aerobic, nonmotile bacillus.iii The high lipid content of this pathogen
accounts for many of its unique clinical characteristics.iv It divides every 16 to 20 hours, which is an extremely slow
rate compared with other bacteria, which usually divide in less than an hour. v Mycobacteria have an outer
membrane lipid bilayer.vi If a Gram stain is performed, MTB either stains very weakly "Gram-positive" or does not
retain dye as a result of the high lipid and mycolic acid content of its cell wall.vii MTB can withstand
weak disinfectants and survive in a dry state for weeks. In nature, the bacterium can grow only within the cells of
a host organism, but M. tuberculosis can be cultured in the laboratory.viii
Clinical presentation
Most children with TB will present with symptoms such as prolonged cough lasting 2 weeks or more; fever >2 weeks,
often associated with poor weight gain; and loss of weight, energy, activity or appetite. Although fever and weight loss
are common in children with extrapulmonary TB, the conspicuous symptoms are usually associated with the site of
disease.ix
Pulmonary
In about 90% of cases tuberculosis infection involves the lungs.x,xi Symptoms may include chest pain and a prolonged
cough. Any child with a history of cough for more than 2 weeks should be reviewed and investigated for TB. Other
common symptoms include night sweats and failure to gain weight or weight loss. About 25% of people may not have
any symptoms (i.e. they remain "asymptomatic").ix
Extrapulmonary
In 15–20% of active cases, the infection spreads outside the respiratory organs, causing other kinds of
TB.xii Extrapulmonary TB occurs more commonly in immunosuppressed persons and young children. In those with
HIV, this occurs in more than 50% of cases.xiii Notable extrapulmonary infection sites include the pleura (in
tuberculous pleurisy), the central nervous system (in tuberculous meningitis), the lymphatic system (in scrofula of the
neck), the genitourinary system (in urogenital tuberculosis), and the bones and joints (in Pott's disease of the spine),
among others. When it spreads to the bones, it is also known as "osseous tuberculosis". xiv a form
of osteomyelitis.ii Sometimes, bursting of a tubercular abscess through skin results in a tuberculous ulcer.xv An ulcer
originating from nearby infected lymph nodes is painless, slowly enlarging and has an appearance of "wash
leather".xvi A potentially more serious, widespread form of TB is called miliary tuberculosis.xvii and makes up about
10% of extrapulmonary cases.xviii
A high index of suspicion is the key to diagnosis of TB in childrenix
Suspect TB disease in a child under the following conditions:
• History of contact with PTB sputum-smear positive in a child who is 5 years or younger.
• Cough of 2 weeks or more
• Unexplained prolonged fever greater than 38 degrees Celsius after exclusion or failure of treatment for usual
diseases such as malaria or pneumonia
• Unexplained loss of weight
• Failure to gain weight
• HIV infection
• Past history of TB treatment
Gilhooley
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Jinja Regional Referral Hospital
Nalufenya Road
Jinja
Uganda
• Non-response to nutritional rehabilitation after at least 2 weeks of proper nutritional care
• Haemoptysis
Signs to look for in a physical examination
• Severe wasting
• Enlarged cervical lymph nodes that may be painful
• Swelling (angulation), also known as gibbus, in the middle of the back
• Pleural effusion
• Progressive deformity of bones or joints
First line investigations and interpretation
The procedure(s) for diagnosing tuberculosis are usually carried out on patients who have symptoms and have
reported to the health facility on their own. After the patient’s history has been taken and a physical exam has been
performed, investigations are carried out. In most cases, sputum specimens (1 spot and 1 early morning) are
examined for AFB. If facilities are available, patients can also be investigated by culture for Mycobacterium
tuberculosis, chest Xray and tissue histology.
The investigations and tests useful in the diagnosis of TB are described below:
1. Ziehl-Neelsen stain: Used to examine sputum specimen or gastric aspiration fluid. This
is reported as +++, ++, +, scanty or negative.
2. Fluorescence microscopy stain: Another method of identifying the bacilli in the
specimen examined.
3. Chest X-ray: Features of chest X-ray consistent with TB disease include miliary picture,
pleural effusion and mediastinal lymph gland enlargement with lung infiltration.
Although the findings of radiology are nonspecific, abnormalities like any heterogeneous
opacities and cavitations, if located in the upper parts of the lung, are more likely to be
caused by TB.
4. Culture for Mycobacterium tuberculosis: Although this is the definitive diagnostic test,
it is expensive and difficult to carry in the general health service. It will be available only
for special situations, such as research and drug-resistant TB.
5. Aspirated serous fluid: Examines pleura peritoneum and pericardium for total protein,
cells (total and differential). This test classifies the fluid into exudate and transudate.
Exudative fluid is caused most frequently by TB in countries with high prevalence of TB
and HIV.
6. Tissue aspirate: Ziehl-Neelsen or fluorescence staining of the aspirate, e.g., lymph node
aspirate.
7. Tissue biopsy: Histology examination to see if morphologically the inflammation is diagnostic of TB.
In a child it is even more difficult to obtain a reliable sample for culture or histology. When seeing a child with
suspected TB it is important to consider the location of the infection and consider investigations appropriate to that
location. Possible locations and investigations are outlined below.
Gilhooley
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Jinja Regional Referral Hospital
Nalufenya Road
Jinja
Uganda
Table 1; sites of possible TB and appropriate investigationix
Gilhooley
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Jinja Regional Referral Hospital
Nalufenya Road
Jinja
Uganda
Initial management
Emergency management
Airway
- ensure if safe.
Breathing
- Cyanosis – give oxygen
- Respiratory distress (indrawing, RR)
Circulation
- Weak pulse/CRT>3 seconds – consider 10mls/kg fluid bolus
- Ensure drinking/BF – if not consider NGT or IV fluids
Disability – AVPU and glucose
- If AVPU = V,P,U consider TB meningitis and need for LP
- Monitor for raised ICP – pupils, eye deviation
- If glucose <2.2 give bolus 10% glucose
- LP if no contraindications.
Exposure
- Check skin, bones, joints, spine
- HIV positive?
Medications used to treat TB
Below is a table showing the different medications used in the treatment of TB and their respective
doses in children.
Table 2; Anti-TB medications and doses
Gilhooley
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March 2013
Jinja Regional Referral Hospital
Nalufenya Road
Jinja
Uganda
Treatment of Tuberculosis
Treatment of TB depends of the category of TB. There are 4 categories and each requires
different. The 4 categories are outlined below.
Table 4: Categorising TBix
Table 3: Anti-TB regimes for each categoryix
Gilhooley
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March 2013
Jinja Regional Referral Hospital
Nalufenya Road
Jinja
Uganda
Monitoring
Health workers providing TB treatment to children should assess progress:



at 2 weeks after start of treatment
at the end of the initial phase of treatment and
monthly thereafter until treatment completion
The child should be assessed for symptoms, treatment adherence, adverse events and weight change. Medication
dosage should be adjusted for any weight gain.
For sputum smear-positive children, sputum should be examined at these points:



end of 2 months
5 months
during the last month of treatment
Chest X-rays are not routinely required for treatment follow-up in children as many children have slow radiological
response to treatment, especially those with hilar and mediastinal adenopathy. A child not responding to anti-TB
treatment in the first 2 months should be referred for further assessment and management. These children may have
drug-resistant TB, unusual complications of pulmonary TB, other causes of lung disease or problems of treatment
adherence.
Education
Parents and children should be made aware of the diagnosis. The background of how the infection was acquired and
the need for prolonged medication should be carefully explained. The need for strict adherence to medications should
be discussed with the parent/carer and the child. Until effective education and counselling has been achieved
anti-TB medications should not be started.
Contact Tracing
Whenever a child is diagnosed as having TB contact tracing should also be performed in order to ensure all exposed
people receive prophylaxis or treatment if necessary.
Children who are at risk of exposure should be evaluated for the possibility of having TB. If on review it is felt they
have TB they should undergo counselling prior to starting the required anti-TB regime in the treatment section. If after
evaluation they are not felt to have TB then they are deemed to be at risk. Children under 5 years or who are HIV
positive are deemed to be at risk and should be given 6 months of Isoniazid prophylaxis (see page 7 for doses).
Children over 5 years of age do not require prophylaxis.
Gilhooley
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March 2013
Jinja Regional Referral Hospital
Nalufenya Road
Jinja
Uganda
Bibliography
i
USAID 2009. Tuberculosis Profile Uganda.
http://www1.usaid.gov/our_work/global_health/id/tuberculosis/countries/africa/uganda.pdf
ii
Kumar V, Abbas AK, Fausto N, Mitchell RN (2007). Robbins Basic Pathology (8th ed.). Saunders Elsevier. pp. 516–522.
Dolin, [edited by] Gerald L. Mandell, John E. Bennett, Raphael (2010).Mandell, Douglas, and Bennett's principles and practice of
infectious diseases (7th ed.). Philadelphia, PA: Churchill Livingstone/Elsevier. pp. Chapter 250
iv Southwick F (10 December 2007). "Chapter 4: Pulmonary Infections". Infectious Diseases: A Clinical Short Course, 2nd ed..
McGraw-Hill Medical Publishing Division.
v indal, editor-in-chief SK. Textbook of pulmonary and critical care medicine. New Delhi: Jaypee Brothers Medical Publishers.
pp. 525.
vi Niederweis M, Danilchanka O, Huff J, Hoffmann C, Engelhardt H (March 2010)."Mycobacterial outer membranes: in search of
proteins". Trends in Microbiology 18(3): 109–16.
vii Madison B (2001). "Application of stains in clinical microbiology". Biotechnic & Histochemistry 76 (3): 119–25.
viii Parish T, Stoker N (1999). "Mycobacteria: bugs and bugbears (two steps forward and one step back)". Molecular
Biotechnology 13 (3): 191–200
ix Uganda Ministry of Health. MINISTRY OF HEALTH MANUAL OF THE NATIONAL TUBERCULOSIS ANDLEPROSY
PROGRAMME. 2nd EDITION 2010.
x Lawn, SD; Zumla, AI (2 July 2011). "Tuberculosis".Lancet 378 (9785): 57–72.
xi Behera, D. (2010). Textbook of pulmonary medicine (2nd ed. ed.). New Delhi: Jaypee Brothers Medical Pub.. pp. 457
xii Jindal, editor-in-chief SK. Textbook of pulmonary and critical care medicine. New Delhi: Jaypee Brothers Medical Publishers.
pp. 549
xiii Golden MP, Vikram HR (2005). "Extrapulmonary tuberculosis: an overview".American Family Physician 72 (9): 1761–8
xiv Kabra, [edited by] Vimlesh Seth, S.K. (2006). Essentials of tuberculosis in children(3rd ed. ed.). New Delhi: Jaypee Bros.
Medical Publishers. pp. 249.
xv Manual of Surgery. Kaplan Publishing. 2008. pp. 75
xvi Burkitt, H. George (2007). Essential Surgery: Problems, Diagnosis & Management 4th ed. pp. 34.
xvii Dolin, [edited by] Gerald L. Mandell, John E. Bennett, Raphael (2010).Mandell, Douglas, and Bennett's principles and practice of
infectious diseases (7th ed.). Philadelphia, PA: Churchill Livingstone/Elsevier. pp. Chapter 250
xviii Ghosh, editors-in-chief, Thomas M. Habermann, Amit K. (2008). Mayo Clinic internal medicine : concise textbook
iii
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