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Transcript
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 2 Epidemiology 3 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 4 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 5 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 6 Interaction between TB and HIV 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 7 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 9 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%) 10 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 11 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 12 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 13 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 14 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 15 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 16 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 17 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 18 PTB X-ray (1) Hilar lymphadenopat hy without parenchymal infiltrate PTB X-ray (2) Hilar lymphadenopat hy with minimal parenchymal infiltrate PTB X-ray (3) Hilar and mediastinal lymphadeno-pathy with parenchymal infiltrate PTB X-ray (4) Right upper lobe infiltrate Hilar lymphadenopathy (arrow) Extrapulmonary TB 23 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 24 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 25 Lymph Node TB (1) Most common form of EPTB Most common locations in HIV patients: • Cervical/supraclavicular • Axillary • Abdominal 26 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 27 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) 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 30 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) 31 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 32 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 33 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) 35 Osteoarticular Disease (2) TB in hip, knee, elbow, ankle • Slow process, with mild pain, stiffness, restrictive movement • Dx: synovial fluid for stain and culture 36 Treatment 37 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 38 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 39 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) - 40 WHO Management of TB in Children 2006 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 41 Treatment monitoring Clinical response and drug sideeffects 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 42 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 43 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 44 IPT: Isoniazid preventive therapy Contraindication Contraindication Presentation absolute Allergy with INH in history: • Fever • Eruption • Hepatitis • Progressive hepatitis, cirrhosis • Neuro-peripheric disease Relative 45 IPT: Isoniazid preventive therapy Regimen 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 46 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 47 Thank you! Questions? 48