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Tuberculosis in Children with HIV/AIDS

Tuberculosis in Children with HIV/AIDS. HAIVN Harvard Medical School AIDS Initiatives in Vietnam. Learning Objectives. By the end of this session, participants should be able to: Recognize clinical signs/symptoms suspicious for TB in HIV-infected children

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Tuberculosis in Children with HIV/AIDS

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  1. Tuberculosis in Children with HIV/AIDS HAIVN Harvard Medical School AIDS Initiatives in Vietnam

  2. 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

  3. Epidemiology

  4. 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

  5. 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 sources WHO fact sheet No104, March 2012

  6. 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

  7. 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

  8. Distributions of PTB and EPTB in HIV-infected Children Pulmonary TB (PTB) 76% Extrapulmonary TB (EPTB) 46% 22% PTB +EPTB A C Hesseling et al. Outcome of HIV infected children with culture confirmed tuberculosis. Arch Dis Child 2005;90:1171–1174.

  9. Pulmonary TB in HIV-infected Children

  10. 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%)

  11. PTB in Children <5 (2)

  12. 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. 7th edition. Chapter 250 Long et al. Principles and practices of pediatric infectious diseases. 3rd edition. Chapter 134

  13. Clinical Presentations

  14. Diagnosis (1) WHO. 2006

  15. 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

  16. 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

  17. 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

  18. 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

  19. PTB X-ray (1) • Hilar lymphadenopathy without parenchymal infiltrate

  20. PTB X-ray (2) Hilar lymphadenopathy with minimal parenchymal infiltrate

  21. PTB X-ray (3) • Hilar and mediastinal lymphadeno-pathy with parenchymal infiltrate

  22. PTB X-ray (4) • Right upper lobe infiltrate • Hilar lymphadenopathy (arrow)

  23. Extrapulmonary TB

  24. 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

  25. 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

  26. Lymph Node TB (1) • Most common form of EPTB • Most common locations in HIV patients: • Cervical/supraclavicular • Axillary • Abdominal

  27. 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

  28. Lymph Node TB: Example Healed scars after treatment 3 year old girl with L cervical lymph node cluster of several month

  29. Abdominal TB Lymphadenitis

  30. 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:

  31. TB Meningitis (2)

  32. 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

  33. 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

  34. Pleural TB (2) TB Empyema • Lymphadenopathy (thin arrows) • Pleural effusion (thick arrows)

  35. 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)

  36. Osteoarticular Disease (2) • TB in hip, knee, elbow, ankle • Slow process, with mild pain, stiffness, restrictive movement • Dx: synovial fluid for stain and culture

  37. Treatment

  38. 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

  39. TB Treatment (1)

  40. TB Treatment (2)Recommended Doses of First-line Anti-TB of Adults and Children WHO Management of TB in Children 2006

  41. 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

  42. 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

  43. 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

  44. 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

  45. IPT: Isoniazid preventive therapyContraindication

  46. IPT: Isoniazid preventive therapyRegimen • 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

  47. 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

  48. Thank you! Questions?

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