Transcript Session 13 - Teaching Slides

Tuberculosis in Children
with HIV/AIDS
HAIVN
Harvard Medical School AIDS
Initiatives in Vietnam
1
Learning Objectives
By the end of this session, participants
should be able to:
 Recognize clinical signs/symptoms
suspicious for TB in HIV-infected
children
 Propose the appropriate work-ups
and treatment for TB
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Epidemiology
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TB in Vietnam
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Vietnam is among the 22 high burden
countries that account for about 80% of
new TB cases per year
In 2010, in the general population
(including HIV positives):
• The incidence is 180/100,000
• The prevalence is 334/100,000

The TB incidence in HIV positive patients
is 43%
WHO Global TB Control Report 2011. www.who.int/tb/data
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TB in Children
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About 1 million children (11%)
develops TB annually
Children < 5, malnutrition, and HIV+
are most at risk for developing TB
Infants is at highest risk
Almost children infected with TB by
active TB in adult
Possibility infected with drug resistance
sources
WHO fact sheet No104, March 2012
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TB in HIV-infected Children

HIV-infected infants:
• have up to 24x higher risk of TB than non HIVinfected

HIV-infected children:
• are more likely to have extra-pulmonary TB or
combination of PTB and EPTB
• have 4x higher risk of acquiring TB if CD4 < 15%

Mortality rate is 6x higher among HIVinfected children
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Interaction between TB and HIV
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TB is one of the most common OIs among HIVinfected children in resource-limited countries
TB infection:
• speeds the progression of HIV by increasing
viral replication
• worsens immunological suppression in HIV
patients
• More severe illness, difficulty of difference
diagnosis with other OIs
HIV increases risk of:
• acquiring primary or reactivation TB
• mortality among patients with TB
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Distributions of PTB and EPTB
in HIV-infected Children
Pulmonary TB
(PTB)
76%
Extrapulmonary
TB (EPTB)
22%
46%
PTB +EPTB
A C Hesseling et al. Outcome of HIV infected children with culture confirmed tuberculosis.
Arch Dis Child 2005;90:1171–1174.
Pulmonary TB in
HIV-infected Children
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PTB in Children < 5 (1)

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In young children <5, infection is
primary
Infants exposed to TB will usually
develop active disease
Miliary-meningeal TB is more
frequent (about 5%)
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PTB in Children <5 (2)
Primary PTB
Progressive
primary TB
• large mediastinal or
• resembling acute
hilar lymph nodes with
pneumonia:
small parenchymal
 acute onset
focus
 variable CXR
• hilar adenopathy with
patterns
lower lobe pneumonitis
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PTB in Adolescents

Resembles adult-type disease:
• Fevers, productive cough, weight loss,
anorexia, hemoptysis
• CXR with upper lobe infiltrates or
cavities
Mandell et al. Principles and practices of infectious disease. 7 th edition. Chapter 250
Long et al. Principles and practices of pediatric infectious diseases. 3 rd edition. Chapter 134
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Clinical Presentations
Triad: fever, cough, weight loss
When these are present, TB should be sought for
Chronic
cough
• unremitting cough not improving after a
course of empirical antibiotics
• present for >14 days
Fever
• body temperature of >38 °C for >14 days
Wasting
(weight loss or failure to thrive)
• No weight gain
• Weight for age < 2 z-score
• Weight loss >5% since the last visit
Diarrhea
• also a frequent symptom
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Diagnosis (1)
Strongly suggestive of TB if 3 or more are present:
Chronic
symptoms
fever, cough, weight loss, diarrhea
Physical
signs
malnutrition, clubbing, pallor, and other
EPTB signs
Tuberculin
skin test
positive tuberculin skin test (≥ 5mm)
Chest X-ray
primary complex, hilar adenopathy,
cavity, miliary pattern, pleural effusion,
any opacity or infiltration not explained by
WHO. 2006
other disease
Household contact with TB
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Diagnosis (2)

Sputum or gastric aspirate x3, or
specimens from affected sites
• Sent for AFB staining, microscopy and
culture
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CXR
PCR (sputum, liquid gastric, spinal
fluid…) negative did not exclude TB
ESR or CRP
CBC (to look for anemia)
AST/ALT
Mantoux test or IDR tends to be negative in HIV+ children,
and is not required for diagnosis 15
Important Considerations
in Diagnosis (1)

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Young children often cannot produce
sputum, instead require gastric
aspiration
The rate of BK+ in gastric aspirate is
about 25-50%
Most pediatric cases are sputum
negative
• Children >6 may have smear positive PTB

Suspect of TB in cases of prolonged
respiratory infection
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Important Considerations
in Diagnosis (2)


Send samples for mycobacterial culture
or other new diagnostic methods (Gene
Xpert) when possible
Mycobacterial culture is extremely
useful to:
• increase diagnostic yield (in smear
negative cases)
• determine sensitivity
• identify multi-drug resistance
• differentiate between MTB and nontuberculous mycobacteria
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Important Considerations
in Diagnosis (3)

Consider drug resistant TB in
children when:
• Close contact with drug resistant source
• Contact with TB patient who died when
on going treatment and suspected drug
resistant TB (non-adherence, relapse,
contact with MDR-TB patient)
• No response with essential TB drug
• Contact with source who have sputum
positive after 2 month of DOTS
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PTB X-ray (1)

Hilar
lymphadenopat
hy without
parenchymal
infiltrate
PTB X-ray (2)
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Hilar
lymphadenopat
hy with
minimal
parenchymal
infiltrate
PTB X-ray (3)

Hilar and
mediastinal
lymphadeno-pathy
with parenchymal
infiltrate
PTB X-ray (4)

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Right upper lobe
infiltrate
Hilar
lymphadenopathy
(arrow)
Extrapulmonary TB
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EPTB: Suggestive Signs (1)
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EPTB present in more than 25 % of
TB in children
Non-painful enlarged cervical
lymphadenopathy with fistula
formation
Meningitis not responding to
antibiotic treatment
Gibbus, especially of recent onset
(vertebral TB)
WHO 2006
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EPTB: Suggestive Signs (2)

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Non-painful enlarged joint
Fluid collection:
• Pleural effusion
• Pericardial effusion
• Distended abdomen with ascites

Signs of tuberculin hypersensitivity:
• phlyctenular conjunctivitis
• erythema nodosum
WHO 2006
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Lymph Node TB (1)
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Most common form of EPTB
Most common locations in HIV
patients:
• Cervical/supraclavicular
• Axillary
• Abdominal
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Lymph Node TB (2)
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Non-tender, firm, fixed to underlying
tissue
Can spread to adjacent nodes
resulting in a clustered mass
Over time, progress to an indurated,
erythematous, non-tender node
which can rupture with draining sinus
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Lymph Node TB: Example
Healed scars after treatment
3 year old girl with L cervical lymph
node cluster of several month
Abdominal TB Lymphadenitis
Clinical
presentations
Diagnosis
Prolonged fevers (on and off)
Prolonged diarrhea (on and off)
Abdominal pain (non-specific)
Weight loss or poor weight gain
With/without:
peripheral lymph nodes
pulmonary TB
• Tend to have low CD4 count
•
•
•
•
•
Ultrasound/CT:
• enlarged para-aortic lymph nodes
• mesenteric lymph nodes 29
TB Meningitis (1)
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Course is usually gradual over several
weeks
Clinical presentation:
Fever
Headache
Vomiting
Drowsiness
progressing to
lethargy to coma
• Nuchal rigidity
•
•
•
•
• Cranial nerve
abnormalities
• Seizures
• Hypertonia
• Hemiplegia
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TB Meningitis (2)
hydrocephalus
basal meningeal enhancement
tuberculoma
cerebral edema
On
imaging
•
•
•
•
CSF
• lymphocytic, 10-500 cells/mm3
• protein to
• glucose to
Dx
• PCR
• stain and culture
• better yield with higher volume of CSF
(10cc or more)
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Miliary TB

Clinical presentation:
• Malaise, anorexia, weight loss with low
grade fever
• Progressing to cough, rales, wheezing,
• Hepatosplenomegaly
• Generalized lymphadenopathy (50%) over
several weeks
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CXR: reticulovascular-miliary pattern
Disseminated to CNS (meningitis) and
abdomen (peritonitis) in 20-40% of
cases
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Pleural TB (1)
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Uncommon in children < 6
Clinical presentation:
• Abrupt onset, with high fever, chest
pain, shortness of breath
• Affected side with dullness to percussion
and diminished breath sounds
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Dx: Pleural fluid or pleural biopsy for
culture. Stain of fluid has low
sensitivity
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Pleural TB (2)
TB Empyema
 Lymphadenopathy
(thin arrows)
 Pleural effusion
(thick arrows)
Osteoarticular Disease (1)

Pott disease: lower thoracic and
upper lumbar vertebrae
• Low grade fever, restlessness, back
pain, refusal to walk
• Surgery may be required for diagnosis
and treatment
• XR: collapse and wedging of vertebral
body, angulation of the spine (gibbus)
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Osteoarticular Disease (2)
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TB in hip, knee, elbow, ankle
• Slow process, with mild pain, stiffness,
restrictive movement
• Dx: synovial fluid for stain and culture
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Treatment
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Principle of TB treatment in
children
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Treatment started when TB is
suspected
Continuing the treatment until the TB
diagnosis is excluded
Flowing DOTS
Combination of TB drug:
• At least 3 drug in intensive phase
• At least 3 drug in maintain phase
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Respect dosage, regular, duration
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TB Treatment (1)
Regimen
2RHEZ/4RH
2SRHEZ/1RHEZ/5RHE
Indication
• For new TB at all forms
• Severe disease: miliary TB, TB
meningitis…
• Relapse TB, failure with the
first regimen, re-treatment
after interruption
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TB Treatment (2)
Recommended Doses of First-line Anti-TB of Adults and Children
Recommended Dose
Drug
Daily
Dose and Range
(mg/kg body
weight)
Isoniazid
Rifampicin
Pyrazinamide
Ethambutol
Streptomycin
3 times weekly
Maximum Dose and Range Maximum
(mg)
(mg/kg body
weight)
(mg)
5 (4-6)
300
10 (8-12)
-
10 (8-12)
600
10 (8-12)
600
25 (20-30)
-
35 (30-40)
-
Children 20 (15-25)
adults 15 (15-20)
-
30 (25-35)
-
15 (12-18)
-
15 (12-18)
-
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WHO Management of TB in Children 2006
Note
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TB active when patient on ART
• Attention with IRIS
• Using ARV simultaneous with TB drug:
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Switch NVP to ABC or EFV if possible
With ART regimen include LPV/r: dosage of
Ritonavir=Lopinavir
• Cotrimoxazole prophylaxis
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Treatment monitoring
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Clinical response and drug sideeffects
Sputum smear:
• Pulmonary TB smear (+):
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At the end of 2nd,3rd, 5th, 7th(or 8th) month
depending on regimen
• Pulmonary TB smear (-):
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At the end of 2nd & 5th
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Treatment monitoring (cont.)
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Chest X-ray:
• Repeat after 2-3 months of treatment
• Hilar should persist up to 2-3 year after
treatment sucessful
• Normally of chest X-ray: continue
treatment until finish the regimen duration
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Iris monitoring:
• Do not stop TB drug
• Consider Corticosteroids
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IPT: Isoniazid preventive therapy
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Indication:
• HIV infected children > 12 months of
age:
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No evidence of active TB and
No contact with TB patient
• HIV infected children < 12 months of
age:
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Only children who have contact with TB
patient
Excluded active TB
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IPT: Isoniazid preventive therapy
Contraindication
Contraindication
Presentation
absolute
Allergy with INH in
history:
• Fever
• Eruption
• Hepatitis
• Progressive
hepatitis, cirrhosis
• Neuro-peripheric
disease
Relative
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IPT: Isoniazid preventive therapy
Regimen
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Isoniazid (INH)
10 mg/kg/day, maximum 300mg
daily
Admission one time/day, on fixe time
and distance of meals
Duration: 6 months
Vitamin B6: 25mg daily
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Key Points
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Always include TB in the differential
diagnosis of respiratory infections,
prolonged fevers, or wasting
PTB’s clinical presentations include
prolonged cough, fevers, and growth
failure
Prolonged fevers, abdominal pain,
diarrhea, and weight loss could be due to
abdominal TB lymphadenitis
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Thank you!
Questions?
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