pediatric tuberculosis

7/21/2019 Pediatric Tuberculosis

1/36

PEDIATRIC TUBERCULOSIS

Hot topics / Unresolved issues inClinical Practice

Ann M. Loeffler, M.D.Legacy Emanuel Childrens Hospital

Portland, ORFaculty Consultant

Francis J. Curry National TB Center

February 28, 2009


2/36

Hot topics / unresolved issues

The continuum between LTBI and TB disease Bacteriologic diagnosis of TB in children

Imaging of pediatric TB suspects Treatment of pediatric TB

Use of and need for EMB

Doses of drugs (more needed)

MDR and MDR-LTBI


3/36

TB vs. LTBI Latent TB infection is defined as a positive TST (or

IGRA) with a normal chest radiograph and no signsor symptoms of TB disease

TB disease suggests metabolically active

populations of M. tuberculosis In pediatrics, common radiographic findings

include intrathoracic lymphadenopathy and

parenchymal changes in any lobe Cavitary disease is unusual before adolescents

Pleural disease is relatively uncommon


4/36

TB vs. LTBI Approximately 50% of children diagnosed with TB

in the developed world are asymptomatic Many have been diagnosed early in their course

(especially during contact investigation of a

contagious adult) In developing countries,

there is limited active case

findings, and essentially all

individuals with TB disease

are symptomatic


5/36

TB vs. LTBI Continuum between LTBI and

TB disease

Early after infection, air space focus andadenopathy (primary complex) seen

Most of these cases involute and can be treated asLTBI

Some are actively replicating and will result insevere disease if not treated


6/36

TB vs. LTBI In the developed world we treat almost any infiltrate or

enlarged intrathoracic lymph node in a TST positive child asTB disease (Even WHO treats isolated LAD as disease)

In early INH studies:

among children with asymptomatic primary TB treated withINH alone, 90% reduction in complications compared to

placebo

Mount NEJM 1961 265; 713-21


7/36

TB vs. LTBI Among placebo recipients: 9% complications in those with

parenchymal changes and 2.5% in those with only LAD

Among 1400 children who received INH only 2 had

definite extrapulmonary progression, 30 intrathoracicprogression

Mount NEJM 1961 265; 713-21


8/36

TB vs. LTBI

To complicate things more: Not all children with culture confirmed

tuberculosis have a positive TST 14% of 200 children had negative TST at dx

5.5% had persistently negative TST (less severe dz)

Some children with normal chest radiographshave positive cultures

Steiner Am J Dis Child. 134:747-50 1980


9/36

TB vs. LTBI - My philosophy Try not to overcall TB on the chest radiograph

Isolated calcification, pleural thickening, andperibronchial cuffing are unlikely to be TB

If it doesnt look like TB - consider treatment ofother causes and repeat a film in a few weeks(monitor closely)

Treat more aggressively: Contacts, TST positive, symptomatic and young

children


10/36

Bacteriologic diagnosis Fewer than 25% of pediatric

cases confirmed by culture

Sputum, gastric aspirates,BAL

CSF

Biopsy specimens

Others


11/36

Gastric aspiration People swallow mucus in

their sleep

Collect gastric contentsbefore the stomach empties

www.nationaltbcenter.edu/pediatric_tb

RESOURCE button at left

has many forms andreferences as well as l ink tothis video instruction


12/36

Gastric aspirate yield

A negative culture does not rule out TB First specimen is the very highest yield

Nearly 100% yield for


13/36

Respiratory specimen yield

Outpatient gastric aspirates 3 California clinics

41% overall yield

48% yield for inpatients

37% yield for outpatients

90% of positives obtained on the first day

Lobato, Loeffler, Furst et al Pediatrics. 102(4):E40, 1998


14/36

Induced sputum vs. gastric aspirates

South Africa

Sputum induction: salbutamol MDI, 15 minnebulized saline, chest PT and NP suctioning

22% yield (n=54)

Gastric aspiration: 20 ml saline, wait 2-3 min

16% yield (n=40)

High rate of smear positive and HIV infected

Zar, Hanslo, Apolles, et al Lancet 365:130-4 2005


15/36

Sputum induction

Induced sputum Ugandan children 12% positive smear and 30% positive

culture in HIV endemic area

Int J TB Lung Dis 9:716-26, 2005


16/36

Nasopharyngeal aspiration

94 children enrolled 8.5% smear and 24% culture pos by NPA

9.6% smear and 22% culture pos by sputuminduction

Owens Arch Dis Child 2007;92:693696


17/36

Other tests

Stool PCR 38% sensitive among culture + children Laryngeal swabs 28% culture positive

String test intriguing Transoesophageal endosonography with fine needle

aspiration

Wolf Am J Trop Med Hyg. 79:893-8, 2008

Thakur An Trop Paed 19 :333-6, 1999Chow F BMC Infect Dis 6:67, 2006


18/36

Bronchoscopy / BAL

Valuable for evaluation of other diagnoses

Evaluation / treatment of airway compression

AFB culture collection


19/36

BAL culture yield

Author Year Region % + cxBAL % +gastric

Cakir 2008 Turkey 12.8% 10%

Bibi 2002 Israel 4% ----

Singh 2000 India 22% 12%

Somu 1995 India 12% 32%

Abadco 1992 USA 10% 50%

Norrman 1988 Scandanavia 21% 12%


20/36

Imaging

Standard of care is two view chest radiograph

CT scan clearly identifies abnormalities notseen on plain film

Most helpful for lymphadenopathy (NEED IV contrast) >80% of children have LAD on CT

37% of patients mangt altered by CT

CT should be reserved for ptswith equivocal dx

Kim AJR 168:1005-9 1997


21/36

Pediatric treatment Pediatric TB is paucibacillary and likely needs less

aggressive treatment to cure

Because the populations are small, there is lessrisk of emergence or amplification of resistance

Many providers use INH & RIF alone for isolatedLAD

Studies show efficacy and tolerability of early twiceweekly regimens for three drug regimen


22/36

Pediatric treatment - ethambutol (EMB)

Providers reluctant to use ethambutol in children due to

difficulty in monitoring optic toxicity

Several reports now support the safety of ethambutol use in

children

Given that the vast majority of children with asymptomaticTB are successfully treated with INH alone - ? Is EMB

necessary

I have been involved in treatment of three children with INH

resistant TB who failed INH, RIF, PZA


23/36

Pediatric treatment - ethambutol (EMB)

Ocular toxicity 40% of adults at 50 mg/kg/dose

0-3% of adults at 15 mg/kg/dose

No well documented cases in children

2 of 3800 children stopped EMB with possible toxicity

Mean peaks markedly lower in children

Doses of at least 20 mg/kg/dose needed

Donald Int J Tuberc Lung Dis10:1318-1330 2006


24/36

Pediatric treatment pyrazinamide (PZA

Children have lower levels of PZA compared to adults

ATS dose 15 30 mg/kg/day 50 mg/kg/ biw

WHO 20 30 mg/kg/day 35 mg/kg/tiw

AAP 20 40 mg/kg/day 50 mg/kg/biw or tiw

I suggest AAP dose

Graham Antimic Agents Chemoth 2006 50:407-13


25/36

Pediatric treatment - PK

Isoniazid Studies show that many children require higher doses of

INH to reach 2 3 mcg/ml Young children require more than older

Fast acetylators in particular at risk

WHO recommends 5 mg/kg

AAP / ATS dose of 10 15 mg/kg probably better

Schaaf Arch Dis Child 2005;90:614-8


26/36

PK - levofloxacin

Fluoroquinolones not used widely in children due toarthropathy observed in puppy models

Large survey of 2500 participants of efficacy trialsshowed rates of musculoskeletal complaints 2.1% vs.0.9% for comparators (p 5 years of age Levofloxacin available IV; tabs: 250, 500, 750 mg and

suspension: 25 mg/ml


27/36

Please paste in

Francis J. Curry National Tuberculosis Center , 2008: Drug-Resistant Tuberculosis: A Survival Guide for Clinicians,

Figure 1, Page 35 www.nationaltbcenter.edu/drtb Second Edition


28/36

Largest series of 38 children with MDR-TB in Peru

Children received 5-7 drugs to which theisolate was susceptible (includinginjectables and fluoroquinolones)

Minimum of 18 - 24mo (12 mo. Cx neg)

94% cure

MDR-TBResistance to at least INH & RIF

Drobac Pediatrics 2006;17:2022-9


29/36

South African experience 36 child contacts to MDR tx for disease

Treatment was mostly oral

4 5 drugs

6 months for isolated LAD; most 9 12 months

Severe disease 12 months from cultureconversion

10% death; 15% default

Schaaf Arch Dis Child 203;88: 1106-11

MDR-TB


30/36

New York experience Extensive disease treated for 18 24 mo

Modest / asymptomatic disease 12 months LTBI treated with two drugs to which the

isolate was susceptible no breakthroughcases (no fluoroquinolones)

MDR-TB & MDR-LTBI

Steiner P Unpublished data


31/36

New York experience 1995 - 2003 20 children with MDR-TB

Average 4.4 drugs for mean 18.8 months 45% treated without an injectable drug

40% treated without a fluoroquinolone One died shortly after starting therapy

MDR-TB

Feja PIDJ 2008;27: 907912


32/36

New York experience 1995 - 2003

51 children with MDR-LTBI

2-7 drugs used (avg 3 drugs) mean 10.3mos

88% COT for children treated in chestclinic compared to 22% not

MDR-LTBI

Feja PIDJ 2008;27: 907912


33/36

South African contacts of MDR-TB TB disease on 20% of untreated children

TB disease in 5% of children tx with 2 drugs

MDR-LTBI


34/36

No studied regimens Most experts recommend using adult type regimens for

TB disease

MDR-LTBI treatment controversial

Given lack of data, many recommend treating only

high risk contacts (conversions, youngest children)

If treating I suggest fluoroquinolone and a second

drug to which the isolate is susceptible (PZA, EMB,

ETH)

Pediatric MDR and MDR-LTBI


35/36

Children are the unreached in many parts of theworld as their early, asymptomatic and not

contagious disease does not get the attention of

the public health machinery

Their identification offers an opportunity to find

and treat a contagious source case

Conclusions


36/36

Unresolved clinical issues include: the difficulty in determining who has true

disease requiring multi-drug treatment vs. who

will control their infection

Difficulty in confirming disease bacteriologically

and confirming drug-susceptibility Optimal doses and regimens for drug

susceptible and drug resistant disease

Conclusions

pediatric tuberculosis

Documents