Tuberculosis in Children

By

JESSE APPEAKORANG
 OUTLINE
• Introduction
• Etiology and Epidemiology
• Pathophysiology
• Clinical Features
• Screening/Diagnosis
• Treatment
• Drug Resistance Tb
• Prevention
 Introduction

• Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis

• TB is common among children and adolescents, and is an important cause of death

especially in young children (< 5 years)

• It is transmitted through air from one person to another mainly via coughing, sneezing

• Young children, especially infants, commonly acquire TB from the adults or

adolescents with infectious TB with whom they are in close contact at home, while older
children and adolescents are also often infected outside the home

• An understanding of the risk factors for TB infection and disease among children and
adolescents is critical for improved prevention and diagnosis.

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SDG 3: Ensure healthy lives and promote wellbeing for all at all ages

End the epidemics of AIDS, tuberculosis, 3.3

malaria
Reduce 3.1 Reduce 3.2 neglected tropical &
Maternal child and diseases and combat
mortality neonatal mortality hepatitis, water-borne

End the epidemics of AIDS, 3.3

and other communicable diseases

Reduce 3.4 tuberculosis,

Strengthen 3.5 malaria Reduce 3.6
mortality due to NCD and improve Prevention and treatment of Mortality
mental health neglected
substance abusetropical
(narcotics,& due to road traffic
diseasesalcohol)
and combat injuries

Universal 3.7
hepatitis, water-borne
Achieve 3.8 Reduce 3.9
access to sexual and and other communicable
universal diseases deaths and illness
reproductive health-care services health coverage due to pollution
and contamination

a Strengthen implementation FCTC .3 b Access to affordable essential.3 c Increased health financing.3 3.d Enhance capacity for early warning,
(tobacco) medicines and technologies and health workforce in risk reduction and management of
developing countries national and global health risks

4
 From exposure
Infection
to disease
Exposur
Disease
e Child or
adolescent Child or
Child or breathes in TB adolescent
adolescent bacteria into his becomes
spends or her lungs, unwell with
then carries live signs and
time with (often dormant) symptoms of
someone bacteria inside TB because
who has the body but the bacteria
infectious remains well are
•
TB disease withwho
Not everyone exposed is infected, and not everyone nois signs ordevelop disease
infected will multiplying
• Majority of children who progress to TB disease do so within 2 years following exposure – with progression to disease most
rapid in infants and young children symptoms of TB
• Children mainly develop primary disease with lymph node involvement while adolescents often develop secondary “adult type”
disease following re-activation
 Difference between TB infection and disease
TB infection TB disease
TB bacilli mainly dormant and locally-contained TB bacilli multiplying and may be spreading, i.e.
dissemination
Person is not sick (no TB symptoms) Person is sick (TB symptoms)
Cannot transmit TB to others Can transmit TB to others
TPT prevents progression to TB disease TB treatment cures disease, prevents death and
stops transmission

• The reality is a spectrum with “latent” infection requiring TPT at one end
and active disease requiring full TB treatment at the other
• It is important to consider the spectrum when ruling out active TB before
initiating treatment for infection or TPT, especially in adolescents

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CONCENSUS DEFINITIONS
 Natural history of TB disease
Exposure to
TB
70-90% 10-30%
No Infection
infection 10%
90%
Active
Latent TB
TB DISEAS
Untreated
E Treated

Never
Die Surviv Di Cure
develop
within e e d
active
2 years
disease
8
 EPIDEMIOLOGY
• TB kills 4,000 people daily
• In 2015, there were an estimated 10.4 million
new (incident) TB cases worldwide, of which 5.9
million (56%) were among men, 3.5 million (34%)
among women
• 1.0 million (10%) among children. People living
with HIV accounted for 1.2 million (11%) of all new
TB cases
 TB among children and adolescents
• Most TB cases are pulmonary TB:
– 75% in younger children
– 90% in older children

• Extra-pulmonary TB (EPTB) presentation varies with age

• Globally, the TB treatment success rate in children (<15 years) is 85%

• Nearly 20% of children with TB die:

– most deaths (80%) are in young children < 5 years
– most deaths (96%) are in children who were not detected and so did not access
treatment

• TB is often misdiagnosed as HIV, pneumonia or malnutrition

10
 WORLD CHILD TB
• Child TB accounted for 1,000,000 new cases in
2015
• 170,000 children died from TB in 2015
The risk of TB disease is higher among young children

12
 TB-associated risks for adolescents

• The risk of exposure to TB and infection increases during adolescence due to more
frequent and wider social contacts

• The risk of developing disease following infection increases during adolescence

• biological changes such as associated with puberty
• the prevalence of at-risk factors increases during adolescence
 Cigarette smoking
 Diabetes
 HIV
 Malnutrition
 Pregnancy

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 CAUSES OF RESURGENCE IN INCIDENCE OF TB:

There has been a resurgence in the incidence of TB

globally in the last 20 years. Factors responsible for
this include:
• Worsening economic situations
• Multidrug resistance
• HIV pandemic
• Large number of displaced persons living in poor conditions
as a result of conflicts and wars
Risk factors for TB infection
and disease in children

For TB infection For TB disease

• Contact with source case • Young age
– Closeness of contact – Especially 0-2 years
– Duration of contact
• HIV infection
– Risk of infection and disease
– Cavities on CXR
• Other immunosuppression
– Malnutrition
• Increased exposure – Post-measles
– Living in high TB endemic
communities
– Children of families living with HIV • Not BCG vaccinated
– Risk of disseminated disease
Child and adolescent TB/HIV

• The risk of TB is higher among HIV-infected children than HIV-uninfected children and
therefore conducting an HIV test for children at risk or with TB is important

• The risk of culture-confirmed TB is 20 times higher in HIV-infected not receiving antiretroviral

therapy (ART) than in HIV-uninfected children

• TB related deaths are higher among HIV–infected children particularly those who are not
receiving ART

• 16% of the TB related deaths in children (0–14 years) are among children living with HIV

• TB and HIV are the major infectious diseases causing death in adolescents globally

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The risk of TB disease and severe TB disease is higher among HIV positive children

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Diagnosis of PTB

Typical symptoms

Cough especially if persistent and not improving

Weight loss or failure to gain weight
Fever and/or night sweats
Fatigue, reduced playfulness, less active

Especially if symptoms persist (>2 weeks) without improvement following

other appropriate therapies (e.g. broad-spectrum antibiotics for cough; anti-
malarial treatment for fever; or nutritional rehabilitation for malnutrition)
Clinical examination for suspected TB
Check weight, record weight and compare to previous weights

Vital signs: temperature and respiratory rate

Respiratory system: signs of respiratory distress

Auscultation and percussion: usually normal but

may reveal lung disease or pleural effusion

Clinical features that might suggest other causes

of chronic lung disease
Growth faltering or failure to thrive
e.g. recurrent cough and/or wheeze responsive
to bronchodilators suggests asthma;
finger clubbing suggests bronchiectasis

Weight loss
Spectrum of Tuberculosis diseases
1- Lymph node enlargement in TB

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 2-Bronchial disease

• 2a- Collapse: complete airway

obstruction due to resorption of
distal air or collapse

• 2b -Partial obstruction causes ball

valve effect and hyper inflation of
the segment of lobe involved .

Carlos M et al, N Eng J Med 367 2012, Carlos M Journal of Infection

(2017) 74 574-583
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 3-Pneumonia 4-Miliary
Disease

• Bronchopneumonic consolidation
• Nodal perforation into an airway with
endobronchial aspiration of bacilli causes
local areas of caseation surrounding the
airways results in a patchy consolidation
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5-Expansile/Pleural Disease

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6- Cavitatory and Pericardial
Disease

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Look beyound the lungs

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 Extra pulmonary tuberculosis – Infants, children and
adolescents
Signs and Symptoms of EPTB depends on the site of disease
Site of EPTB Typical clinical presentation

1. TB adenitis Asymmetrical, painless, non-tender lymph node enlargement

Enlargement is usually visible and persistent, more than one month
+/- discharging sinus

Most commonly in neck area

2. Pleural TB Dullness on percussion and reduced breath sounds

+/-chest pain some children may be completey asymptomatic

Usually young (< 5 years) with disseminated disease and severely ill

3. TB meningitis Headache, irritability/abnormal behaviour, vomiting (without diarrhoea),

lethargic/reduced level of consciousness, convulsions, neck stiffness,
bulging fontanelle, cranial nerve palsies

4. Miliary TB Non-specific, lethargic, fever, wasted

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 Extra pulmonary tuberculosis - Children and adolescents
Signs and Symptoms of EPTB depends on the site of disease

Site of EPTB Typical clinical presentation

Usually 5 years and older

5. Abdominal TB Abdominal swelling with ascites or abdominal masses,

usually painless
6. Spinal TB Deformity of spine
May have lower limb weakness/paralysis/unable to walk

7. Pericardial TB Symptoms of cardiac failure

8. TB bone and Swelling end of long bones with limitation of movement

joint Unilateral effusion of usually knee or hip

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 POTT’S DISEASE
L3 collape Same patient
Recommended approach to
diagnose TB in children
WHO Guidance for NTP on management of TB in children

1. Careful history
includes history of TB contact
symptoms suggestive of TB
2. Clinical examination
includes growth assessment
3. Tuberculin skin test
4. Bacteriological confirmation whenever possible
5. Investigations relevant for suspected PTB or suspected
EPTB
6. HIV testing
Period between primary and the appearance of clinical evidence
of various forms of TB

• Pulmonary tuberculosis – within a few months of primary infection.

• Miliary and meningeal tuberculosis – 2-6 months.
• TB adenitis - 3-9 months.
• Bones and joints – several years.
• Renal and genital tuberculosis – may take over a decade.
• Pulmonary lesions occurring as a result of reactivation of a dormant
tuberculosis focus previously established in the body takes a number
of years after primary infection.
TB Screeing tool used by NTP in
Ghana

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 DIAGNOSIS

•TB diagnosis is either by bacteriological confirmation or clinical diagnosis

•Access to diagnostic tests for TB in Ghana continues to evolove

•Central/urban>peripheral/rural; tertiary>secondary>primary

•For TB diagnostic tests, consider availability, clinical indications, and utility

of the particular test and the overall diagnostic pathways or approaches in use

•Xpert should be always used as the initial diagnostic test in children

given its higher sensitivity

•Lack of availability of a TB diagnostic test should not hinder the diagnosis of

TB in children

•A negative TB diagnostic test does not exclude TB

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 DIAGNOSIS

Investigation Type of sample Rationale

Xpert MTB/RIF* Sputum, expectorated or induced or Higher sensitivity and
from other samples e.g. gastric specificity compared to
aspirate/lavage, nasopharyngeal smear microscopy
aspirate, stool Detects rifampicin-
resistant (or presumptive
Lymph node aspirate (+ biopsy) MDR) TB
Xpert MTB/RIF Ultra* (new, 2019) Cerebrospinal fluid Xpert MTB/RIF Ultra has
higher sensitivity than
N.B. Other specimens such as pleural Xpert MTB/RIF and also
Xpert MTB/XDR (new, 2020) fluid, pericardial fluid, joint aspirate or detects rifampicin
ascites can be sent for investigation resistance
but are very low yield Xpert MTB/XDR detects
resistance to a range of
drugs including isoniazid
and fluoroquinolones

Smear microscopy Sputum, Lymph node aspirate Sensitivity or yield very low
and Xpert
preferred/recommended if
available
Sensitivity increases in
adolescents

* WHO recommended initial TB diagnostic tests 36

 Xpert performance on pediatric respiratory samples and on
lymph node fine needle aspirates
Form of TB Sample type Xpert sensitivity Xpert specificity
(reference standard: (reference standard:
culture) culture)

Expectorated 62% 98%

sputum
Pulmonary TB Induced sputum 62% 98%
(PTB) (IS)
Gastric Aspirate 66% 98%
(GA)
Nasopharyngeal 46% 98 - 100%
aspirate (NPA)

Stool 61% 98 - 100%

TB Fine needle 80 % - 93.5% , , 69.2% - 93.8% , ,
lymphadenitis Aspiration (FNA)

37
POSEE sample collection budgeting tool
The Gene Xpert machine

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 Tuberculin skin test
• TST is useful to support a diagnosis of TB in children with suggestive clinical
• features who are sputum smear negative or who cannot produce sputum
•  A positive TST indicates infection:
• o positive in any child if ≥ 10 mm irrespective of BCG immunisation
• o also positive if ≥ 5 mm in HIV-infected or severely malnourished child
•  A positive TST is particularly useful to indicate TB infection when there is no
• known TB exposure on clinical assessment i.e. no positive contact history
•  Caution
• o A positive TST does not distinguish between TB infection and active
• disease
• o A negative TST does not exclude TB disease
TUBERCULIN SKIN TEST (MANTOUX TEST)
Other important diagnostic tests commonly indicated
in the evaluation of TB

Investigation Eligibility (If test is available) Rationale

HIV test Children and adolescents with HIV is a risk factor for TB disease
presumptive or diagnosed TB and severe disease

Testing should be guided by A positive HIV test guides

country specific HIV guidelines additional management (ART,
CPT)

Chest Children who are unable to CXR is useful in children especially

radiography produce sputum since they have primary disease
(CXR)
Children and adolescents who Features suggestive of TB :- hilar
have a negative sputum test adenopathy, miliary picture,
result cavitation, effusion

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 TREATMENT OF TUBERCULOSIS
• Steps in Effective Anti-TB Treatment
– Make a diagnosis. Determine whom to treat.
– Make a case definition. Define the type of TB case
– Supervise and Monitor treatment. Ensure patient
completes treatment, i.e. prevent default.
 TREATMENT OF TUBERCULOSIS
Mode of Action of Anti-TB Drugs
• Bactericidal Drugs
– Isoniazid
– Rifampicin
– Pyrazinamide
– Streptomycin
• Sterilising action (killing all the bacilli particularly the
persisters)
– Rifampicin (most effective)
– Pyrazinamide
• Prevention of drug resistance
– Isoniazid
– Rifampicin
 Current WHO recommended treatment regimens for TB in
children in low HIV prevalence and low isoniazid resistance
settings*

TB diagnostic category Intensive phase Continuation phase

• Smear or Xpert -negative pulmonary TB 2 RHZ 4RH

• Intrathoracic lymph node TB
• Tuberculous peripheral lymphadenitis

• Extensive pulmonary disease 2RHZE 4RH

• Smear or Xpert - positive pulmonary TB
• Severe forms of extrapulmonary TB (other than
tuberculous meningitis/osteoarticular TB)

• Tuberculous meningitis and osteoarticular TB 2RHZE 10RH

• * Settings with low HIV prevalence are defined as those in which the HIV prevalence is
≤1% among adult pregnant women or ≤5% among TB patients. WHO Guidance, 2014.

44
 Current WHO recommended TB treatment regimens for TB in
children in high HIV prevalence or high Isoniazid resistance
settings (or both)*

TB diagnostic category Intensive phase Continuation phase

All forms of TB except 2 RHZE 4RH

tuberculous meningitis
and osteoarticular TB

Tuberculous meningitis 2RHZE 10RH

and osteoarticular TB

• * Settings with high HIV prevalence are defined as those in which the HIV prevalence is
≥1% among adult pregnant women or ≥5% among TB patients. WHO Guidance, 2014

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NEW REGIMEN
 MAJOR SIDE EFFECTS
Drug Side effect
Isoniazid Peripheral neuritis
Hepatotoxicity
Psychosis

Rifampicin Orange discoloration urine and tears

Gastrointestinal disturbance
Hepatotoxicity
Thrombocytopenia
Pyrazinamide Hyperuricaemia
Skin rash
Hepatotoxicity

Ethambutol Optic neuritis

Hepatotoxicity
Streptomycin Toxicity to 8th nerve
Rash
Renal damage
 Example: Guidance on management of side effects

Side effects Clinical presentation Main Anti TB Management

medicineinvolved
Peripheral neuropathy (early Burning sensation; pins and needles Isoniazid Pyridoxine
or late side effect) mainly in hands and feet
Liver Toxicity Nausea; Vomiting; Yellow coloration of Pyrazinamide STOP all drugs and REFER the child
eyes; Right sided abdominal pain; Right Rifampicin Isoniazid
hypochondriac tenderness; Hepatomegaly
Gastrointestinal Nausea, Vomiting, Abdominal All Manage the symptoms as they come and
dysfunction discomfort counsel the patient
Hypersensitivity (usually Skin rash Rifampicin Isoniazid Anti-histamine if mild: if severe STOP all drugs and
early side effect) Pyrazinamide REFER the child
Central nervous system Irritability; Psychosis; Drowsiness; Isoniazid Pyridoxine given as preventive therapy and
dysfunction Seizures treatment for INH toxicity. STOP INH in case
of seizures and Refer.
Anaemia Palor of mucus membranes; Signs of heart Rifampicin Manage the anaemia using IMCI or clinical
failure in severe cases. care guidelines.

Visual problems Blurred or impaired vision Ethambutol STOP Ethambutol and REFER the child. Continue
with RHZ
Athralgia Joint pains Pyrazinamide GIVE analgesics e.g. paracetamol
Red urine Red urine Rifampicin Re-assure the care giver or child or adolescent
and continue treatment

NTLP Uganda, 2015

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 PREVENTION(PEP)
• CHILDREN 5 YEARS AND BELOW WITH
HISTORY OF FAMILY CONTACT ARE GIVEN
ISONIAZID 10mg/kg/daily for 6 months.
• FULL TREATMENT IS GIVEN WHEN THERE IS
EVIDENCE OF DISEASE
 Indication for corticosteroid

1. Large pleural effusion

2. Endobronchial tuberculosis

3. Pericardial effusion

4. Tuberculous meningitis

5. Laryngeal tuberculosis
 Supportive Therapy

• Improved Nutrition
• Screening of immediate family members
• Surgical intervention where necessary
 Monitoring TB treatment response (1)

Monitoring Components
Clinical - Majority of children will be monitored clinically
Monitoring - Check for symptom resolution and weight gain
- Measure the weight at each clinic visit and adjust the dosage
accordingly
- Establish treatment support and monitor adherence
- Pharmacovigilance: elicit and manage adverse events as per guidelines
- Advise immediate cessation of treatment and review if evidence or
concerns of hepatotoxicity
- Refer children and adolescents with treatment failure or severe adverse
event for further management

52
 Monitoring TB treatment response (2)

Monitoring Components

Laboratory monitoring - Check for sputum conversion using microscopy for children and
adolescents diagnosed with bacteriologically confirmed TB as per
national recommendations
- Younger children who are not able to provide a sputum sample for
monitoring can be followed up clinically

• CXR is not routinely required in follow-up to monitor treatment

response if the child is responding well clinically to TB treatment

• Note that lymph nodes – cervical or perihilar on CXR – may remain

enlarged even at the time of completion of treatment, but this does
not necessarily indicate treatment failure

53
• Children with TB usually respond well with symptomatic improvement during
intensive phase and good outcome
• A poor response to TB treatment may indicate:
– Poor adherence
– Incorrect diagnosis
– TB due to drug-resistant organism
– Incorrect dosages
– Co-morbidities not managed e.g. HIV
• HIV-infected children and adolescents with TB show poorer response to TB treatment
and require ART and CPT as well as TB treatment
• Successful establishment of effective treatment for TB will rapidly reduce risk of
ongoing transmission

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Newborn Infant of a mother with Tuberculosis:
 TB treatment outcome definitions

Outcome Definition

Cured A pulmonary TB patient with bacteriologically confirmed TB at the beginning of treatment who was smear or
culture negative in the last month of treatment and on at least one previous occasion.

Treatment completed A TB patient who completed treatment without evidence of failure BUT with no record to show that sputum
smear or culture results in the last month of treatment and on at least one previous occasion were negative,
either because tests were not done or because results are unavailable.

Treatment failed A TB patient whose sputum smear or culture is positive at month 5 or later during treatment.

Died A TB patient who dies for any reason before starting or during the course of treatment.

Lost to follow-up A TB patient who did not start treatment or whose treatment was interrupted for 2 consecutive months or
more

Not-evaluated A TB patient for whom no treatment outcome is assigned. This includes transferred out to another treatment
unit as well as cases for whom the treatment outcome is unknown to the reporting unit

Treatment success The sum of cured and treatment completed.

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TB Treatment Card

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DRUG RESISTANCE
 DEFINITIONS
• DR-TB
– Sputum smear or culture positive and has bacilli that are
resistant to first-line TB medications
• Acquired Resistance
– DR in a patient who has received anti-TB for more than
one month and the resistance was during weak or
inadequate therapy
• Primary R: DR in a patient who has never received
anti-TB in past or has received txt < 1 month
 Definitions 2
• Mono-R
– Resistance from only one from first-line antiTB
drugs: eg S, HRZE
• Poly-R
– Resistance to at least two drugs but not to both
HR
• MDR-TB
– Resistance to at least HR
 Summary of drug groups used to treat drug-resistant TB

Drug group Drug name Daily dosage in mg/kg Maximum dose (mg)

a
Group 1: oral first line drugs Ethambutol 20-25 2000
Pyrazinamide 30-40 2000
b
Group 2: injectable agents.
Aminoglycosides
Amikacin 15-20 1000
Cyclic polypeptide Kanamycin 15-20 1000
Capreomycin 15-20 1000

b
Group 3: fluoroquinolones Ofloxacin 15-20 800
Levofloxacin 7.5-10 750
Moxifloxacin 7.5-10 400

Group 4: second line oral

c
Ethionamide (or 15-20 1000
drugs prothionamide)
Cycloserine (or terizidone) 10-20 1000
e
Para-aminosalicylic acid
(PAS; 4 gr satchets) 150 12g

d
Group 5: drugs of uncertain High dose INH 15-20 400
value f
LInezolid 10-12 twice daily 300 once/twice daily
Amoxicillin/clavulanate 15 amoxicillin 3x daily
Clarithromycin 7.5-15 twice daily 500 twice daily
g
Thioacetazone 3-4 150
Imipenem/ cilastatin (only IV)
Clofazimine 3-5 300
Treatment regimens for children with MDR-TB follow the same principles as
in adults

• With extensive pulmonary or disseminated extrapulmonary disease, a minimum of

4 drugs should be included in the regimen
• Use first-line drugs (Group 1) to which DST results show susceptibility for the
duration of therapy
• Add an injectable agent from Group 2 normally given for a minimum of 6 months
and for 4 months after culture conversion. Preferably an aminoglycoside such as
amikacin. Do not use streptomycin unless other second-line Group 2 drugs are not
available
• Add a fluoroquinolone from Group 3 for the duration of therapy. Levofloxacin and
moxifloxacin are preferred to ofloxacin. Note that ciprofloxacin is not
recommended.
• Two to three second-line agents (ethionamide/prothionamide, para-aminosalicylic
acid or cycloserine/terizidone) from Group 4 should be added for the duration of
therapy
• If these groups are not sufficient to build an acceptable regimen of 4 active drugs,
at least 2 drugs from group 5 could be added.
 Observation of drug side effects
• Staff education to recognize side effects;
• Patient should be informed about side effects;
• Monitoring monthly;
• All side effect should be registered;
 Information before treatment
initiation
• History of concomitant diseases or condition
which can contribute of occurrence of drug
intolerance ;
• Adverse drug reactions before;
• Allergic reactions;
• Complete blood account and urine analysis;
 Information before treatment initiation

• Biochemistry: hepatic enzymes, bilirubun,

creatinine, electrolytes baseline;
• Vision acuity, color vision;
• Audiometry;
 Routine testing- Monthly
• Complete blood count, blood urea nitrogen and serum
creatinine,
• Serum potassium:
 Low risk patients first 3 Months, then 2-3 months,
 For high risk patients every 2 weeks than monthly
Hepatic function tests (transaminase, bilirubin )
Psychiatric and audiometric evaluations;
 Extra testing –depending on
symptoms

• Psychiatrist consultation

• TSH

• Other laboratory analyses are performed when indicated by patients

symptoms
 PREVENTION

• TB prevention is one of the priority strategies in TB control

• Increasing attention is being given to prevention within the End TB Strategy

• Recommended approaches for TB prevention include:-

– BCG vaccination
– Contact screening and management
o Improved active TB case finding and management
o TB Preventive Treatment (TPT) – also known as treatment of TB infection – for eligible
contacts and PLHIV
– TB Infection control

68
Prevention of TB in a community

1. Case-finding and effective treatment.

2. Contact tracing and INH chemoprophylaxis.
3. BCG vaccination.
4. Improvement in the general standard of living.
 DOTS
directly observed
therapy, shortcourse

Mycobacterium tuberculosis

vaccines
preventive therapy
 THANK YOU !!!

LET’S STOP TB TOGETHER