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• Review
• TB in children
• Diagnosis
• Treatment
• Prevention
Risk for TB infection and disease

The diagnosis of childhood tuberculosis in low/intermediate burden settings Dr. Anne Detjen Desmond Tutu TB
Centre, Cape Town and
Dr. Klaus Magdorf Charite University Hospital, Berlin

• Highly contagious infection and disease caused by

exposureto M. tuberculosis

• Etiologic agent: M. tuberculosis

• Gram (+) bacterium
• Aerobic, non-motile slightly curved or straight
• Retain carbolfuchsin dye acid-fast bacilli

• Mode of transmission: airborne route


• Infection takes place by way of the lower respiratory

tract lung is the first organ involved

• Disease is usually the result of dissemination from an

initial primary focus

• TB in children is an indicator of recent and on going

transmission of M. tuberculosis in the community

• Primary Infection most patients are asymptomatic


• Spread by airborne droplet nuclei 1-5 µm

• Expelled when person with infectious TB coughs, sneezes,

speaks, or sings

• Close contacts at highest risk of becoming infected

• Transmission occurs from person with infectious TB

disease (not latent TB)

 Pulmonary TB
• Latent TB infection (LTBI)
 Extra-pulmonary TB
• TB adenitis
• TB of bones and joints
• Cutaneous TB, scrofuloderma, erythema nodosum
• Ocular TB
 Manifestation can be predicted:
• Pulmonary: months after primary infectionS
• Miliary, TB Meningitis, Diss TB: 26mos
• TB adenitis: 3-9 mos
• Bones & joints: 1 year
• Renal: 5-25 yrs
TB EXPOSURE – a condition in which child is in
close contact with contagious adult or adolescent TB
cases, but without any signs and symptoms of TB ,
with negative TST reaction, and no radiologic and
laboratory findings suggestive of TB

TB Infection or Latent TB Infection (LTBI) – a

condition in which a child has no signs and symptoms
of presumptive TB nor radiologic or laboratory
evidence, but has a positive TST reaction
TB DISEASE – a presumptive TB who after clinical
and diagnostic evaluation (TST and radiologic) is
confirmed to have TB

- classification is either based on the

bacteriological status or on the anatomical site
TB Disease Registration Group

NEW- patient who has never had treatment for TB or

who has taken anti-TB drugs for < 1 month
- Treatment after failure
- Treatment after lost to follow up (TALF)
- Previous treatment outcome unknown
OTHER- patient who do not fit into any of the
categories listed above

RELAPSE A patient previously treated for

TB who has been declared cured,
or completed treatment in their
most recent treatment episode,
and is presently diagnosed with
bacteriologically- confirmed or
clinically diagnosed TB
Treatment after Failure A patient who has been preciously
treated for TB and whose treatment
failed at the of their most recent course:
* A patient whose sputum smear or
culture is positive at 5 months or later
during treatment
* A clinically diagnosed patient for
whom sputum examination cannot be
done and who does not show clinical
improvement anytime during treatment

Treatment after lost to follow up A patient who has previously

(TALF) treated for TB but was lost to
follow up for > 2 months in their
most recent course of treatment
and is curently diagnosed whether
bacteriologically 0r clinically –
confirmed TB
Previous Treatment, outcome unknown Patient who has been previously treated
(PTOU) for TB but whose outcome after their
most recent course of treatment are
unkwon or undocumented
Classification of TB Disease

 Based on Bacteriologic Status

• Bacteriologically confirmed (by DSSM, culture,

or rapid diagnostic test – Xpert MTB/RIF)

• Clinically diagnosed – does not fulfil the

criteria for bacteriologic confirmation but has
been diagnosed with active TB Disease
Classification of TB Disease

 Based on Anatomic Site


Classification of TB Disease

 Based on History of Previous Treatment

• New case

• Retreatment

 IPT is not considered as previous treatment

Classification of TB Disease

 Based on HIV Status

- HIV- negative Patient –refers to any
bacteriologically-confirmed or clinically diagnosed
case of TB who has a negative result from HIV testing
at the time of TB diagnosis

- HIV- positive patient – refers to any

bacteriologically- confirmed or clinically diagnosed
case of TB who has positive result from HIV testing at
the time of TB diagnosis
Classification of TB Disease

 Based on Drug Susceptibility Testing

Monoresistant TB – resistant to one first-line
anti TB drug only
Polydrug-resistant TB – resistance to more
than one first-line anti TB drug (other
than both isoniazid and rifampicin)
Multidrug-resistant TB (MDR-TB) –
resistance to at least both isoniazid an
Classification of TB Disease

 Based on Drug Susceptibility Testing

Extensively drug resistant TB (XDR-TB)
- resistance to any fluoroquinolone and to
at least one of three second- line injectable
drugs ( capreomycin, kanamycin, amikacin), in
addition to multidrug resistance

Rifampicin-resistant TB (RR-TB) – resistance

to rifampicin , detected using phenotypic or genotypic
methods, with or without resistance to other anti-TB drugs
- it includes any resistance to rifampicin , whether
monoresistance , multidrug resistance, polydrug resistance
or extensive drug resistance
Criteria for Diagnosis of TB

 Positive culture with or without a positive smear for

M. tuberculosis is the GOLD STANDARD for the
diagnosis of TB

 In the absence of bacteriological evidence--> a child

is presumed to have active TB if 3 or more of the
following criteria are present
Criteria for Diagnosis of TB

- exposure to an adult/ adolescent with active TB
- signs and symptoms suggestive of TB
- positive Tuberculin Test
- abnormal chest radiograph suggestive of TB
- laboratory findings suggestive of TB ( histological,
cytological, biochemical, immunological and/or
Symptomatic child

(3 out of 6 criteria: PPS/ DOH / WHO

 Cough or wheezing of ≥ 2
TB symptomatic) weeks / 21 days
 Fever - >38 °C for 14 days
 Weight loss or failure to
 Fatigue, reduced playfulness,
or lethargy
 Failure to respond to 2 weeks
of appropriate antibiotic
 Failure to regain previous
state of health after 2
weeks of a viral infection or

 Organ-specific symptoms
Exposure to a TB case

 Exposure?  Close contact - living in

 Does anyone in the the same household or
home have TB? in frequent contact with
 Has your child been in
a source case with
contact with anyone smear-positive PTB.
with TB?  Children are infectious
if smear (+) or with
cavitary TB
 Make an effort to find
the source case and
other undiagnosed
Tuberculin Skin Test

 TST interpretation depends on two factors:

 diameter of the induration;

 person’s risk of being infected with TB and risk of

progression to disease if infected.
Tuberculin Skin Test

 A positive TST has an induration of:

 ≥10 mm: in all other children (whether they have received
BCG vaccination or not)
 ≥5mm in immunocompromised individuals (HIV-infected
children and those severely malnourished; in the presence
of history of close contact, clinical findings suggestive of
TB, CXR suggestive of TB )


Policy recommendation: IGRAs

 Principle: T-cells of
individuals with TB
infection secrete IFN-
γ in response to re-
stimulation with M.
tb-specific antigens
Policy recommendation: IGRAs
Overall conclusions
 Insufficient data and low quality evidence on the
performance of IGRAs in low- and middle-income
countries, typically those with a high TB and/or HIV
 IGRAs and the TST cannot accurately predict the risk of
infected individuals developing active TB disease
 Neither IGRAs nor the TST should be used for the
diagnosis of active TB disease
 IGRAs are more costly and technically complex to do than
the TST.
 Given comparable performance but increased cost,
replacing the TST by IGRAs as a public health intervention
in resource-constrained settings is not recommended.
Chest Radiography and other investigations

 The commonest picture: persistent opacification in
the lung together with enlarged hilar or subcarinal
lymph glands.
 A miliary pattern of opacification children is highly
suggestive of TB.
 Adolescents:
 large pleural effusions and apical infiltrates with cavity formation
being the most common forms of presentation (similar to
 may also develop primary disease with hilar adenopathy and
collapse lesions visible on CXR.

A. For 15 years old and above, with any of:

1. Cough of at least 2 weeks with or w/o

-significant, unintentional weight loss;

-fever;hemoptysis; chest/back pains;
-easy fatigability/malaise; night sweats;
-shortness of breath/difficult breathing
2. Unexplained cough of any duration in:

•a close contact of a known TB case

•high-risk clinical groups (HIV)

3. CXR findings suggestive of TB

(w or w/o symptoms)
B. For those below 15 years old, with any of:

1. At least 3 of the following criteria:

• cough/wheezing x 2 weeks or more
• unexplained fever x 2 weeks or more
• loss of weight/failure to gain weight/loss of appetite
• failure to respond to 2 weeks of appropriate Tx for
• failure to regain previous state of health 2 weeks after
a viral infection or exanthem
• fatigue, reduced playfulness, lethargy
2. Any 1 of the above in a child who is a close contact of a
known active TB case

3. CXR findings suggestive of TB

(w or w/o symptoms)
4. Presumptive extra-pulmonary TB, any of:
-Cough of at least 2 weeks in > or = 15 years

-Child with any 3/6 criteria for TB

-Chest x-ray suggestive of tuberculosis

-Cough of any duration in a high-risk individual, in high-risk

populations, or a close contact of an active TB case
Presumptive DRTB

Any person whether adult or child, who belongs to any

of the DRTB high-risk groups, such as:

-new TB cases that are contacts of confirmed DRTB

cases or non-converter of Category I
-people living with HIV with signs and symptoms of
- re-treatment cases

 Primary diagnostic tool in NTP case finding

 Done in those with presumptive TB who could

expectorate (whether pulmonary or extrapulmonary)

 Should be done prior to treatment initiation

 2 sputa of good quality are collected (spot-spot one

hour apart or spot-early am collected within 3 days),
5-10 ml
Xpert MTB/Rif

 Rapid diagnostic test used for TB diagnosis among:

- Smear negative adults, with CXR findings

suggestive of TB
- Smear negative children
- Presumptive DRTB
- PLHIV with Sg/Sx of TB
MD or TBDC Basis for Treatment

 For children < 15 y/o, decision based on 3/5:

- Clinical signs and symptoms (3/6)

- Exposure to an active TB case
- Positive TST
- Other laboratory findings
Treatment Principles

 All diagnosed TB cases shall be provided with

adequate and appropriate treatment promptly

 Treatment shall be done through a patient-centered,

directly observed treatment to foster adherence
 Treatment shall be based on anatomical site,
bacteriologic status including drug resistance, and
history of previous treatment

 All retreatment patients should be screened for

MDR-TB before treatment initiation

 Anti-TB regimen shall be comprised of at least 4

first-line drugs
Category of tretment Classification and Treatment
Registration Group
Category I Pulmonary TB, new (whether 2HRZE/ 4HR
bacteriologically or clinically
Extrapulmonary, New ,
except CNS, BONES or

Category Ia Extrapulmonary T, New 2HRZE/10HR

Category II Pulmonary or EPTB, 2HRZES/ 2 HRZE / 5HR
previously treated drug
susceptible TB
(relapse,treatment after
failure, treatment afer lost to
follow up (TALF), Previous
treatment outcome unknown

Category IIa EPTB, previusly treated 2 HRZES/ 1HRZE/ 9 HRE

drug-susceptible, CNS,
Mg/kg/day REACTION

Isoniazid (H) C: 10 (10-15) mkD Bactericidal Hepatitis, peripheral

(max 300mg/day neuropthy
A: 5 (4-6)mkD (max

Rifampicin (R) C:15 (10-20) mkD (max Inhibits DNA- Hepatitis,

600mg/day) dependent RNA hypersensitivity
A: 10 (8-12) (max polymerase reaction, orange
600mg/day) discoloration of body

Pyrazinamide (Z) C:30 (20-40) mkD (max Disruption of membrane Most common cause of
2g/day) energy metabolism hepatotoxicity in
A: 25 (20-30)mkD regimens containg H
and R

Ethambutol (E) C: 20 (15-25) mkD (max Inhibits transferase retrobulbar Optic

1.2g /day) enzymes involved in cell neuritis( impairment of
: 15 (15-20) mkD wall synthesis visual acuity and red
green color vision)
Second-line anti-TB drugs
Drug Daily dose MOA Adverse
Mg/kg/day reaction/interac
Amikacin 15-30 mkD OD Bactericidal, Cranial nerve 8
IM/IV inhibits protein damage
Kanamycin 15-30 mkD IM/IV sysnthesis (ototoxicity)

Streptomycin 20-40 mkD IM

Ofloxacin 5 yrs and below 15- Bactericidal; Arthropathy
20 mkD PO inhibits DNA
splitinto 2 divided gyrase
Over 5 years: 10-15
mkD OD
levofloxacin 7.5 -10 PO
moxifloxacin 7.5-10 PO (max
Adjunct Management

– most beneficial when host inflammation
reaction contributes significantly to tissue damage or
impairment of organ functions
- benefits od corticosteroids has been evaluated
in the following forms of complicated TB
* TB Meningitis
* TB pericarditis
* TB Pleural effusion
* Endobronchial TB
* Miliary TB

 TB incidence, prevalence and mortality rates show

decreasing trends globally and in the Philippines

 MDG and STOP TB goals for TB incidence and

mortality will likely be achieved but halving of
prevalence rate is unlikely by 2015

 There is greater attention to other populations /

forms of TB and not just smear (+) cases (TB in
children, in prisons and all forms of TB)

 Diagnosis of TB pulmonary disease in children

still relies on history, TST and radiologic findings

 Importance of contact investigation is highlighted

 LPA and GX are used to screen for MDR-TB in

adults, adolescents and older children

 Usefulness of rapid tests in childhood TB remains

to be seen