Presentation on theme: "MANAGEMENT OF TB-HIV CO-INFECTION BY"— Presentation transcript:
1 MANAGEMENT OF TB-HIV CO-INFECTION BY THE RESPIRATORY/INFECTIOUS DISEASE UNIT,UCTH, CALABAR
2 TUBERCULOSIS IN CHILDREN It is commonly asked why young children with tb are not infectious.They generally have a closed infectionThey do not have significant cough.They lack tussive force necessary to suspend infectious particles in the air.When cough is present children rarely produce sputumWhen sputum is produced, organisms are sparse because they are in low concentration in the endobronchial secretions of children.
3 Diagnosis of TB in children- The Traditional Diagnostic prerequisites Combination of :Contact with infectious adult caseSymptoms and signsPositive tuberculin skin test (TST)Suspicious CXRBacteriological confirmationSerology
4 List of symptoms that may suggest TB in children: Fever (Low or high grade), not responding to anti-malaria treatmentWeight loss, Static weight or failure to gain weightFailure to thriveRecent febrile illness with rash & desquamation (measles, persistent/continuous cough with vomiting (pertussis)
5 List of Suggestive Symptoms,continued Loss of appetiteLymph node swellingsAngle deformity of the spine (back swelling)Joint or bone swellingsNeck stiffness, vomiting, convulsions, impaired conscious (TB meningitis)
6 List of possible Physical signs Chronically or s’tmes acutely ill looking +/- pallorSmall weight for the age (underweight), or features of PEMDiscrete, or matted, frequently non-tender cervical lymphadenopathyFeatures of co-existing HIV or immunocompromised statusHypersensitivity parameters, eg Phlycternular conjuctivitis, Erythema NodosumManifestations of Primary Pulmonary Disease (primary complex, bronchial)Chest signs, or features of Extra-pulmonary TB.
7 TB Diagnosis in children & “value” of score charts In some countries, score charts are used for the diagnosis of TB in children but have rarely been evaluated or validated against a “gold standard” Marais BJ. Arch Dis child 2005;90:Score charts also perform poorly in PTB and HIV infected children!Key features suggestive of TBThe presence of 3 or more of the following should strongly suggest a diagnosis of TB:- Chronic symptoms suggestive of TB- Physical signs highly suggestive of TB- Positive TST- CXR suggestive of TB
9 Manifestations of TB in children >70% of children who develop TB disease have pulmonary manifestations, but ~25 – 35% may have an extrapulmonary presentationThe most common extrapulmonary form is lymph node TB accounting for about 2/3 of cases of extrapulmonary TB2nd most common form is meningeal disease occurring in 13% of patients
10 TB-HIV COINFECTION Manifestations of co-existent HIV-infection: Persistent generalized lymphadenopathy, respiratory illnesses like pharyngotonsilitis, otitis media, mastoiditis, pneumonias, painless parotid enlargement.Gastrointestinal conditions like oropharyngeal candidiasis, diarrhoea, vomiting
12 Other pointers of HIV infection: Oral: Herpes simplex, oral thrush, oral hairy leucoplakiaCutaneous: Chickenpox, molluscum contangiosum- Delayed developmental milestonesSevere progressive encephalopathy
13 History - Evaluation - Chronic cough > 21 days Careful history (including carefully extracting a history of TB contact)Symptoms: commonest:- Chronic cough > 21 days- Fever T > 38oC for 14 days after excluding common causes, such as malaria or pneumonia- Wt loss or FTTSome children with TB infection may not develop any signs or symptoms at any time
21 Clinical features of HIV infection and associated conditions Severe wastingNon-specific dermatitisNational Paediatric ART Training Slides Unit
22 Clinical features of HIV infection and associated conditions cont…. Dermatomal Herpes zosterNational Paediatric ART Training Slides Unit
23 Clinical features of HIV infection and associated conditions cont…. Oral candidiasisNational Paediatric ART Training Slides Unit
24 Tuberculin Skin Testing (TST) TST is the method used for detecting whether an individual has come in contact with the TB bacilli.The TST used is the Mantoux test, containing 5 tuberculin units administered intradermally.The test is read as mm of induration at 48 to 72 hours.
25 Mantoux TestA positive test occurs when a person is infected with M. tb but does not necessarily indicate diseaseInterpretation:- 0 – 4mm = negative- 5 – 9mm = borderline- ≥ 10mm = positive in all other children irrespective of the BCG vaccination- ≥ 5mm = positive in HIV infected children and severely malnourished children (marasmus, kwashiorkor)Useful in screening household contacts with TBFewer HIV infected children will have a positive TSTTST may be negative initially but positive after 2-3 mo of treatment
26 Chest Radiograph as a diagnostic tool of TB Spectrum of radiolographic changes depends on the stage of the disease & the nature of the intrathoracic complicationsThere are no pathognomonic radiological signs of tuberculosis; other lung lesions (viral, bacterial & fungal LIP & IPH) can mimic those of pulmonary TB.Additional radiographs like cervical, spinal/vertebral & abdominal may also be required
27 Chest Radiograph as a diagnostic tool of TB - 2 Certain radiological lesions may however suggest PTB:- Miliary mottling- Hilar or paratracheal lymphadenopathy- ± parenchymal involvement- Collapse consolidation- Pleural effusionCavitatory lesions are rare, but should nevertheless be looked for,Rarely chest X-ray may be normal
30 14/06/12-Homogenous opacity on the right lung field sparing the right perihilar region with loss of cardiac and diaphragmatic silhouettes and mediastinal shift to the left(pleural effusion). Patchy opacities are noted on the left lung field with blunting of the left costophrenic angle. Cardiac size cannot be assessed. Bony thorax appears normal.Radiological Conclusion: Atypical pneumonia with bilateral pleural effusion RT>>Lt.?PTB14/06/12
32 29/06/12-Bilateral widespread diffuse patchy opacities with background groundglass haziness obscuring the right cardiac border and hemidiaphragm including the ipsilateral costophrenic angle. Wideninmg of the superior mediastinum noted. ?Reactive thymic hyperplasia ? Adenopathy. A loculated homogenous opacity in the right upper lung zone with a lamellar component along the distal right coastal margin suggestive of loculated effusion with pleural adhgesions.Radiological conclusion:Atypical pneumonia ? Tuberculosis
33 Previosly generalised patchy opacities with bilateral pleural effusion Rt>>Lt with mediastinal shift to the left ( see 14/06/12). Progressively there has been some reduction in the quantity of pleural fluid on the right but no significant change in parenchymal consolidative changes. Near homogenous opacities obliterating the cardiac and diaphragmatic silhouettes. Recently (see 10/07/12), the effusion on the left is worsening. Cardiac size cannot be fully assessed.Impression:Tuberculous pneumonia with effusion in a background of HIV
37 Is this Miliary TB? No, it’s varicella pneumonia!
38 Bacteriological diagnosis in children Isolation of TB bacilli from clinical specimens remains the gold standard for diagnosisIsolation in children is more difficult than in adults, as they have paucibacillary diseaseThe yield of the organism is low even in the best centres (<50%).
39 Specimen collection 2. Gastric aspiration (fasting, early morning) 1. Sputum :- 10 years or older who can expectorate an on the spot specimen, an early morning specimen and another on the spot specimen2. Gastric aspiration (fasting, early morning)- Aspiration of gastric contents should be performed fasting, ideally while still recumbent after overnight sleep.- Therefore usually performed in hospitalized patients.- Strict adherence to the recommended collection techniques improves the yield of the procedure, as does the collection of specimens on three consecutive days.
40 Specimen collection-1 3. Induced sputum The use of nebulized hypertonic saline to induce coughing allows the production of respiratory specimens in children who cannot expectorate voluntarilyYield from 1 induced sputum specimen = 3 daily gastric aspirates, and is ↑ further by repeated procedures149 children hospitalized pneumonia, Zar 2000median age 9 (3-30) monthsIS in 142 (95%)Induced Sputum positive in 15(10.6%) vs 9 Gastric Lavage (6.3%), p=0.08
41 Specimen collection -2 Broncho-alveolar lavage Fine needle aspiration (FNA): of enlarged glands for AFB and cytology – has a high bacteriological yield6. Biopsy
42 Other diagnostic parameters FBC and ESR- may be normal but commonly leucocytosis with a relative lymphocytosis and a high ESRBCG testNormal BCG evolutionAccelerated BCG reaction
44 Lipoarabinomannan (LAM) assay Antigen capture ELISA assays for the detection of lipoarabinomannan (LAM) in sputum and urine samples has shown promise in suspected TB adults (Boehme C et al, Trans Roy Soc Trop Med Hyg 2005;99: )LAM is a cell wall lipopolysaccharide antigen specific for M. tuberculosisReleased from metabolically active or degrading cellsSecreted intact in urineResults are rapid, typically within 2-3 hours76.5% sensitive in smear negative cases, 80.3% sensitive overall, 99% specificPerforms well in the HIV-infected subgroup
45 Interferon Gamma Release assays (IGRA) New in-vitro test which measures interferon production by T-cellsPrinciple: sensitised T cells produce interferon when mycobacterial Ags are encounteredM. tuberculosis-specific AgsAvailable IGRA-based Tests:1. Quantiferon-TB- IFN production (pg/ml)2. T SPOT-TB- Detects number T cells producing IFN
46 TST vs IFN assays: traditional vs novel TST IFNSensitivity %* %*Specificity % %Cross react BCG Yes NoCross react NTM Yes NoBoosting Yes NoCost Low ModeratePatient visitsLab no yes* Less in the immunocompromised(Nahid, Proc Am Thorac Soc, 2006)
47 Concerns with IFN assays Cannot distinguish latent from active diseaseFew studies in children? efficacy in very young/ HIV/ high incidence TB countriesDiscordance with TST results – Pai Lancet Infect Dis 2004, Mahomed IJTLD 2006? impact of TB treatmentNeed for laboratoryCostPromising and more sensitive than TST
48 Other Newer M. tuberculosis detection methods BACTEC offer slightly superior sensitivity and reduced turn around times compared with conventional Loweinstein –Jensen medium (LJ-medium)MODS( microscopic observation drug susceptibility assay) 8 days to culture positivitylimited utility in childrenPCR: limited utility in children and low sensitivity in paucibacillary TBNAAT (nucleic acid amplification test) rapid test (WHO endorsed): 100minsTB fluorescence microscopyGene expert tb test
50 TB/HIV co-infection in children Should HIV testing be done in all children suspected of having TB (Yes)Should all HIV+ve children be screened for TB? (Yes)How do you differentiate HIV associated lung disease from TB disease?Can children with HIV lung disease also have TB disease? (Yes)
52 Anti-TB treatment: 2 phases Intensive phase - to rapidly eliminate majority of bacilli - to prevent emergence of drug resistanceContinuation phase - to eradicate dormant organismsEither phase can be given daily or 3-times weekly.
53 Main objectives in TB Rx To rapidly kill most bacilli in order to: - stop disease progression - prevent transmission of infectionTo effect cure and prevent relapse (eliminate dormant bacilli)To do the above with minimal adverse reactionTo prevent development of drug-resistant organisms
54 Desirable Characteristics of Drugs BactericidalGood sterilizing activityPrevent of drug-resistanceLow toxicity
57 Codes for TB Rx regimens 2SHRZ/4H3R3Number in front of each phase = duration in monthsLetters = abbreviated drugsSubscript numbers following a letter = number of doses per week of that drug.If no subscript = drug is daily
58 Treatment: WHO category I New smear positive PTBNew smear negative PTB with extensive parenchymal involvementSevere forms of extraPTBSevere concomitant HIV diseaseTreatment- 2HRZE, 4HR or 6HETB Meningitis- 2HRZS, 4HR
59 Treatment: WHO category II Previously treated smear positive PTB- Relapse- Treatment interruption-RAD- Treatment failureTreatment- 2HRZES/1HRZE 5HRE
60 Other Basic Principles Combination therapy - alwaysUse fixed dose combination drugs if possibleDOTS – directly observed therapy, short courseUninterrupted drug supplyChildren with severe forms of TB (meningitis, disseminated, TB spine, and TB pericarditis) should have streptomycin added during the intensive phase
61 Pharmacological challenges RifampicinDecreases the plasma level of Nevirapine (37%), efavirenz (25%), not enough info on dosage adjustment in children. RMP can be used with EFV in children over 3yearsDecreases plasma level of all PIs Lopinavir(75%) ritonavir(35%) (LPV/r, Kaletra, Aluvia),Decreases plasma level of Zidovudine, abacavir
62 First line anti-TB drugs: Adverse effects Drugs Adverse eventsIsoniazid Skin rash, hepatotoxic, peripheral neuritis,psychosisRifampicin Hepatoxic, red urine, anorexia, nausea, abdominal pain, thrombocytopenia, drug interactionsPyrazinamide Hepatotoxic, arthralgiaEthambutol Optic neuritisStreptomycin Rash, anaphylaxis, oto- and nephrotoxic
63 Drug-resistant Tb; Definitions Mono-drug resistance: Resistance to single drugPoly-drug resistance: Resistance to 2 or more drugs, but not to both INH and RMPMDR TB: Resistance to INH & RMP +/- other drugsXDR TB: MDR & 2nd-line injectable & quinolonePrimary resistance: No previous anti-TB Rx or less than 1 monthAcquired resistance: Previous anti-TB Rx >1 month
64 Drugs resistant TB… (contd) WHO estimated that 511 000 new cases of MDR-TB occurred in 2007, 4.9% of all TB casesContribution of Nigeria largely unknownLately, Rifampicin mono-resistance seems on the increase in especially HIV-infected adults
65 Causes of Drug Resistant TB Poor management of drug-susceptible or mono-resistant TB casese.g. incorrect regimens, interrupting treatment (drug supplies, poor bio-availibility), poor adherence by patientsPoor management of MDR-TB cases leads to transmission of MDR-TB strainse.g. late diagnosis, not doing DST in relapse/retreatment cases, poor infection control measures especially in high prevalence HIV settings
66 MDR-TB in childrenDisease (>90%) in children usually develops within 12 months of infectionThis has to be confirmed with DST and DNA-fingerprintingContact tracing and follow-up of children exposed to MDR/XDR-TB should receive high priority
67 2nd-line drugs - WHO Reserve Drugs Ethionamide/prothionamideOfloxacin/levofloxacin/moxifloxacinCycloserine/terizidoneKanamycin/amikacinCapreomycinPara-amino salicylic acid
68 REFERENCESProceedings from the Technical Consultation Workshop on Improving Management of Tuberculosis in children-June, 2010NTBLCP 2010 guidelinesPaediatric ART guidelines 2010