Download presentation
Presentation is loading. Please wait.
Published byCharlene Little Modified over 5 years ago
1
DR SAUMU WAYUWA KPA ANNUAL SCIENTIFIC CONFERENCE 2019
DRUG RESISTANT TB IN CHILDREN DR SAUMU WAYUWA KPA ANNUAL SCIENTIFIC CONFERENCE 2019
2
OUTLINE Resistance patterns Epidemiology MDR TB in children Diagnosis
Management
3
TB RESISTANCE PATTERNS
Mono-resistant TB Resistant to any one drug. Poly-resistant TB Resistant to more than one drug but not both isoniazid and rifampicin. Multi-drug resistant (MDR) TB Resistant to at least both isoniazid and rifampicin. Extensive drug resistant (XDR) TB Resistant to rifampicin, isoniazid, an injectable and a quinolone.
4
BACILLARY POPULATIONS
1. Rapidly multiplying bacilli - Optimum medium: Extracellular. PH 6.5-7, maximum oxygenation (cavity wall) - Large number of bacilli → High probability of spontaneous mutations and natural resistance 2. Slowly multiplying bacilli - Intramacrophagic location. Acid pH. Population<105 Relapse capacity 3. Intermittently growing bacilli - Unfavourable conditions. Solid caseum. Extracellular - Population <105. Relapse capacity 4. Bacilli in latent state: Not susceptible to drugs - Reactivations and relapses
5
M. TUBERCULOSIS RESISTANCE
Natural resistance – characteristic of the bacilli Acquired resistance – therapy problem (resistance in previously treated patients) Primary resistance – transmission problem (resistance in previously untreated patients)
6
DR TB TRENDS IN KENYA
7
GLOBAL EPIDEMIC MDR-TB SITUATION
WHO Reports 2014, 2015, 2016 and 2017 Since 2013, more than 50% of new cases of MDR-TB were among people who have never been treated for TB before, highlighting the importance of transmission and the lack of appropriate infection control measures, particularly at community level
8
MDR-TB IN CHILDREN Is mainly primary (transmitted) drug resistance
Disease in children usually (>90%) develops within 12 months of infection Is more difficult to acquire because of the paucibacillary nature of primary disease Possible if cavitary pulmonary disease Children with DR TB are not major contributors to the spread of DR TB in the community Good source for surveillance on drug resistant TB May reflect the transmission of these organisms in the community
9
MDR-TB IN CHILDREN Children at high risk
Contacts of patients with MDR-TB Living in MDR-TB high prevalence areas
10
RATES OF MDR-TB AMONG CONTACTS OF MDR-TB PATIENTS
Study Country Number of contacts Percentage of patients with MDR-TB (# of TB case/total # with active TB) Kritski et al. (1996) Brazil 218 62% (8/13) Schaaf et al. (2000) South Africa 149 83% (5/6) Texeira et al. (2001) 133 Schaaf et al. (2002) 119 75% (3/4) Bayona et al (2003) Peru 945 84% (35/42)
11
MDR-TB IN CHILDREN Further suspect drug-resistant TB:
If a child gets worse on treatment or fails despite adherence to treatment If an adult index case with unknown susceptibility pattern is: a treatment failure (sputum smear positive after 5 months treatment) a retreatment case a chronic TB case (TB despite 2 previous treatment courses)
12
Drug-susceptible vs. drug-resistant TB in children
DIAGNOSIS OF MDR-TB IN CHILDREN Drug-susceptible vs. drug-resistant TB in children No clinical or radiological difference between these two groups Clinical features and chest radiography does not distinguish DS from DR/MDR TB Confirmed MDR TB is a laboratory diagnosis
13
DIAGNOSIS OF MDR-TB IN CHILDREN
Confirmed DR TB is a laboratory diagnosis : nucleic acid amplification test (e.g. Xpert MTB/RIF) or culture with DST Bacteriological diagnosis should always be attempted for drug sensitivity testing Probable DR TB is diagnosed in a child with active TB disease and a recent close contact with DR TB Suspected DR TB is when a child fails to improve while adherent to first-line anti-TB treatment OR if the adult source case is a treatment failure, a retreatment case or recently died from TB
14
DIAGNOSIS OF MDR-TB IN CHILDREN
Bacteriologic confirmation of TB is more difficult Lower bacillary load Less forceful cough Difficult to obtain specimens More extra pulmonary cases (< 5 years) Important role for X-ray film Gene Xpert is a useful tool
15
DIAGNOSIS OF MDR TB History of contact/previous treatment Sputum smear
Drug Susceptibility Test (DST) - Molecular DST Gene xpert LPA - Conventional DST Liquid culture (MGIT) Solid culture
16
BASELINE LABORATORY INVESTIGATIONS
Sputum smear, FLD and SLD LPA, culture and DST Hemogram UECr LFTs TSH HIV CXR Audiometry ECG
17
DR TB CLINICAL REVIEW County physician, Pediatrician, CTLC/SCTLC, CASCO, Pharmacist, Lab technologist, Nutritionist, Social worker, PHO, psychologist Review team meets at central facility at county/sub county level Patients brought by their facility DOTs nurse/clinician Team reviews the following; Patient’s progress Patient`s suspected or documented ADR`s Sputum smears and cultures Biochemistry lab results Deliberations and notes recorded in patient log book
18
PRINCIPLES OF MANAGEMENT OF MDR-TB IN CHILDREN
The same principles apply as for adults. Do not add a single drug to a failing regimen At least 4 susceptible drugs. Lower bacillary load Probably enough with only 3 drugs?? Use the adult index case’s isolate DST pattern if no isolate from child is available Favorable treatment outcomes: adverse reactions are very infrequent, even with SLD Caution with Bdq <6 years and Dlm <3 years Longer oral or shorter MDR/RR-TB regimens - weight based dosing
19
DESIRABLE CHARACTERISTICS OF DRUGS
Adapted from: Caminero JA, et al. Treatment of TB. Eur Respir Monogr 2012; 58: 154–166 Caminero et al. Treatment of drug-susceptible and drug-resistant TB. Eur Respir Monograph 2018: Bactericidal – to rapidly eliminate the bulk of active bacilli INH, RIF, Lfx/Mfx, SLD Inject, Lzd, Bdq, Dlm 2. “Sterilization” – killing dormant or intermittent growing bacilli RIF, PZA, hMfx, Lfx, Lzd, Cfz, Bdq, Dlm 3. Prevention of Resistance with drug combination 4. Minimal Toxicity
20
WHO RECOMMENDATIONS FOR DR-TB TREATMENT
WHO 2011 update WHO 2016 update
21
Group Medicine Abbreviation
WHO DR-TB Guidelines Grouping Medicines for use in Longer MDR-TB Regimens Group Medicine Abbreviation Group A Include all three medicines (unless they cannot be used) Levofloxacin o Moxifloxacin Lfx Mfx Bedaquiline Bdq Linezolid Lzd Group B Add both medicines Clofazimine Cfz Cycloserine or Terizidone Cs Trd Group C Add to complete the regimen and when medicines from Group A and B cannot be used Ethambutol E Delamanid Dlm Pyrazinamide Z Imipenem/cilastatin or Meropenem Ipm/Cln Mpn Amikacin or (Streptomycin) Am (S) Ethionamide or Prothionamide Eto Pto p-aminosalicylic acid PAS
22
MDR TB TREATMENT REGIMENS
Short term regimen Intensive phase 4-6 Km-Mfx-Pto-Cfz-E-Z-Hhigh-dose Continuation phase 5 Mfx-Cfz-Z-E Individualized regimen
23
CLINICAL AND LABORATORY FOLLOW UP
Month Clinical consult Smear Culture DST LFTs* UECs TSH Chest X-Ray Start √ 1 Every 2 Weeks 2 3 4 Monthly Quarterly but monthly for HIV infected patients Where Indicated 5 6 7 8 9 Every 3 months 10 11 12 Till Completion Every 6 months
24
OUTCOMES OF MDR-TB TREATMENT IN CHILDREN
Systematic review and meta-analysis reviewed treatment outcomes for children with MDR-TB. Eight studies, which reported outcomes on 315 patients, contributed to the database. Average duration of treatment ranged from 6 months to 34 months. The pooled estimate for treatment success (defined as a composite of cure and completion) was 81.7% with death in 5.9%, and default in 6.2% of patients. Adverse reactions occurred in 39.1% of the children, the most common of which were nausea and vomiting followed by hearing loss, psychiatric effects and hypothyroidism. Ettehad D, Schaaf HS, Seddon JA, Cooke GS, Ford N. Treatment outcomes for children with multidrug-resistant tuberculosis: a systematic review and meta-analysis. Lancet Infect Dis 2012;12: Good treatment outcomes due to paucibacillary disease and DOTS (as compared to adults with high bacilli load/presence of cavities making treatment difficult-resistance selection)
25
SUMMARY OF MANAGEMENT OF MDR-TB IN CHILDREN
Confirm MDR TB… if possible Management and review by DR TB clinical review team Use the adult index case’s isolate DST pattern if no isolate from child is available Give at least 4 or more drugs to which the patient’s isolate is susceptible to and/or naïve Counsel parents at every visit about possible adverse events, and the importance of adherence to treatment DOT with daily treatment is essential Close Follow-up is essential: clinical, radiologic and cultures
26
THANK YOU
Similar presentations
© 2025 SlidePlayer.com. Inc.
All rights reserved.