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Tuberculosis in Children with HIV/AIDS

HAIVNHarvard Medical School AIDS

Initiatives in Vietnam

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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

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

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

sourcesWHO 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 HIV-

infected 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 HIV-infected

children

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Interaction between TB and HIV

TB is one of the most common OIs among HIV-infected 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

Distributions of PTB and EPTB in HIV-infected Children

A C Hesseling et al. Outcome of HIV infected children with culture confirmed tuberculosis. Arch Dis Child 2005;90:1171–1174.

Pulmonary TB(PTB)

76%

Extrapulmonary TB (EPTB)

46%22%

PTB +EPTB

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Pulmonary TB in HIV-infected Children

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PTB in Children < 5 (1)

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 PTBProgressiveprimary TB

• large mediastinal or hilar lymph nodes with small parenchymal focus

• hilar adenopathy with lower lobe pneumonitis

• resembling acute pneumonia: acute onset variable CXR

patterns

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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 250Long 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)

WHO. 2006

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 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 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

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Important Considerations in Diagnosis (1)

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 non-

tuberculous mycobacteria

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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

Important Considerations in Diagnosis (3)

PTB X-ray (1)

Hilar lymphadenopathy without parenchymal infiltrate

Hilar lymphadenopathy with minimal parenchymal infiltrate

PTB X-ray (2)

PTB X-ray (3)

Hilar and mediastinal lymphadeno-pathy with parenchymal infiltrate

PTB X-ray (4)

Right upper lobe infiltrate

Hilar lymphadenopathy (arrow)

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Extrapulmonary TB

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EPTB: Suggestive Signs (1)

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)

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)

Most common form of EPTB Most common locations in HIV

patients: • Cervical/supraclavicular• Axillary • Abdominal

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Lymph Node TB (2)

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

Lymph Node TB: Example

3 year old girl with L cervical lymph node cluster of several month

Healed scars after treatment

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Abdominal TB Lymphadenitis

Clinical presentations

• Prolonged fevers (on and off)• Prolonged diarrhea (on and off)• Abdominal pain (non-specific)• Weight loss or poor weight gain• With/without:

peripheral lymph nodespulmonary TB

• Tend to have low CD4 count

DiagnosisUltrasound/CT:• enlarged para-aortic lymph nodes• mesenteric lymph nodes

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TB Meningitis (1)

• Fever• Headache• Vomiting• Drowsiness

progressing to lethargy to coma

• Nuchal rigidity

• Cranial nerve abnormalities

• Seizures• Hypertonia• Hemiplegia

Course is usually gradual over several weeks

Clinical presentation:

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TB Meningitis (2)

On imaging

• hydrocephalus• basal meningeal enhancement• tuberculoma• cerebral edema

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 CXR: reticulovascular-miliary pattern Disseminated to CNS (meningitis) and

abdomen (peritonitis) in 20-40% of cases

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Pleural TB (1)

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

Dx: Pleural fluid or pleural biopsy for culture. Stain of fluid has low sensitivity

Pleural TB (2)

TB EmpyemaLymphadenopathy (thin arrows)Pleural effusion (thick arrows)

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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)

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

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

Respect dosage, regular, duration

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Regimen Indication

2RHEZ/4RH • For new TB at all forms

2SRHEZ/1RHEZ/5RHE

• Severe disease: miliary TB, TB meningitis…

• Relapse TB, failure with the first regimen, re-treatment after interruption

TB Treatment (1)

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TB Treatment (2)Recommended Doses of First-line Anti-TB of Adults and Children

Drug

Recommended Dose

Daily 3 times weekly

Dose and Range(mg/kg body

weight)

Maximum(mg)

Dose and Range

(mg/kg body weight)

Maximum(mg)

Isoniazid 5 (4-6) 300 10 (8-12) -

Rifampicin 10 (8-12) 600 10 (8-12) 600

Pyrazinamide 25 (20-30) - 35 (30-40) -

Ethambutol Children 20 (15-25)adults 15 (15-20)

- 30 (25-35) -

Streptomycin 15 (12-18) - 15 (12-18) -

WHO Management of TB in Children 2006

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Note

TB active when patient on ART• Attention with IRIS• Using ARV simultaneous with TB drug:

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

Clinical response and drug side-effects

Sputum smear:• Pulmonary TB smear (+):

At the end of 2nd,3rd, 5th, 7th(or 8th) month depending on regimen

• Pulmonary TB smear (-): At the end of 2nd & 5th

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Treatment monitoring (cont.)

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 Iris monitoring:

• Do not stop TB drug• Consider Corticosteroids

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IPT: Isoniazid preventive therapy

Indication:• HIV infected children > 12 months of

age: No evidence of active TB and No contact with TB patient

• HIV infected children < 12 months of age:

Only children who have contact with TB patient

Excluded active TB

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IPT: Isoniazid preventive therapyContraindication

Contraindication Presentation

absolute Allergy with INH in history:•Fever•Eruption •Hepatitis

Relative • Progressive hepatitis, cirrhosis

• Neuro-peripheric disease

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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

IPT: Isoniazid preventive therapyRegimen

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Key Points

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?