QUICK REFERENCE FOR HEALTHCARE PROVIDERS
Ministry of Health Malaysia Academy of Medicine Malaysia Malaysian Thoracic Society
Management of Tuberculosis (Third Edition)
2
KEY MESSAGES
1. Tuberculosis (TB) is a notifiable infectious disease. Timely diagnosis, prompttreatment&adherencetomedicationarekeyfactorsincombatingTB.
2. ScreeningofTBshouldbedoneinhighriskgroupsincludingallclosecontacts(especiallyhouseholdcontacts).
3. Patients with symptoms of TB should have sputum smear for acid fast bacilli(AFB),mycobacterium culture & sensitivity (C&S), & chest x-ray (CXR) done.Nucleic Acid Amplification Tests (NAAT) plays a role in rapid detection ofMycobacterium tuberculosis & multidrug-resistantTB(MDR-TB).
4. TB serology should not be used to diagnose pulmonary TB (PTB) orextrapulmonarytuberculosis(EPTB).
5. ForlatentTBinfection(LTBI),tuberculinskintest(TST)isthepreferredmethodfordiagnosis.InterferonGammaReleaseAssaymaybeusedasanalternative.Treatmentshouldbeconsideredforhighriskpatients.
6. AdailyantiTBregimenisrecommendedforbothintensive&maintenancephases.Aproperdefaultertracingsystemshouldbeinplacetodetectearlyinterruptionintreatmentandfollow-up.PoorlymanagedTBwillleadtodrug-resistantTB.
7. Fixed-DoseCombinations are preferred to separate-drugs combination for thetreatmentofTB.
8. Infants & children under 5 years of agewith close contact are at high risk ofdevelopingactiveTB.
9. ActiveTBshouldberuledoutinallHIV-positivepatients.
10. PreventivemeasuresshouldbeemployedtoreduceTBriskamonghealthcareworkers.
ThisQuickReferenceprovideskeymessagesandasummaryofthemainrecommendationsintheClinicalPracticeGuidelines(CPG)ManagementofTuberculosis(3rdEdition).
Detailsof theevidencesupporting these recommendations canbe found in theaboveCPG,availableonthefollowingwebsites:MinistryofHealthMalaysia:www.moh.gov.myAcademyofMedicineMalaysia:www.acadmed.org.myMalaysianThoracicSociety:www.mts.org.my
CLINICAL PRACTICE GUIDELINES SECRETARIATHealthTechnologyAssessmentSection
MedicalDevelopmentDivisionMinistryofHealthMalaysia
4thFloor,BlockE1,ParcelE,62590PutrajayaTel:603-88831246E-mail:[email protected]
Management of Tuberculosis (Third Edition)
3
HIGH RISK GROUPS
• Close TB contacts especially infants & children under 5 years of age• Immunocompromised patients such as those with diabetes mellitus, HIV
infection, end-stage renal disease, malnutrition, use of immunosuppressant drugs, etc.
• Intravenous drug users• People
• •
• • living in overcrowded conditions
INVESTIGATIONS • PTB
o CXR (PA) should be taken in symptomatic & high risk patients. Any abnormality warrants further diagnostic investigation.
o A minimum of 2 sputum samples (including 1 early morning sample) should be sent for TB microscopy. One sample should be subjected to M. tuberculosis C&S testing.
o Spontaneously produced sputum is generally used for laboratory testing; however sputum induction could be carried out if patient is unable to expectorate.
o NAAT can be carried out for the rapid of M. tuberculosis and detection of MDR-TB. This test can be carried out in a TB risk level 2 laboratory.
• EPTBo Patient with EPTB should have a CXR to exclude or co-existing
PTB. Imaging (ultrasound, computerised tomography & magnetic resonance imaging) may be carried on the area of interest to demonstrate features suggestive of TB.
o Body or tissue samples suspected of TB should be subjected to TB C&S.
o NAAT testing can be carried out on positive TB cultures.
TREATMENT FOR NEW TB CASES
• For
• Fixed-Dose Combinations (FDCs) are preferred to separate-drugs combination
newly-diagnosed PTB, the standard antiTB treatment is a 6-month regimen consisting of daily 2-month of EHRZ followed by daily 4-month of HR.
Dosages of First-Line AntiTB Drugs
Drug
Recommended doseDaily 3 times per week
Dose (range) in mg/kg
body weight
Maximum in mg
Dose (range)in mg/kg
body weight
Daily maximum
in mgIsoniazid (H)* 5 (4 - 6) 300 10 (8 - 12) 900Rifampicin (R) 10 (8 - 12) 600 10 (8 - 12) 600Pyrazinamide (Z) 25 (20 - 30) 2000 35 (30 - 40)** 3000**Ethambutol (E) 15 (15 - 20) 1600 30 (25 - 35)** 2400**Streptomycin (S) 15 (12 - 18) 1000 15 (12 - 18)** 1500**
*Pyridoxine 10 - 50 mg daily needs to be added. **Daily treatment is the preferred regimen.
for the treatment of TB.
Management of Tuberculosis (Third Edition)
4
• Any deviation from the standard regimen or previously treated TB should bereferredtospecialistwithexperienceinTBmanagement.
• Durationoftreatmentmaybeprolongedincertaincircumstances:-o PersistentlyAFBsmearpositiveafter2months o EPTBo ExtensivecavitationonCXR
LATENT TB INFECTION• Only individuals who are at high risk of acquiring LTBI or developing TB
reactivationshouldbeinvestigated.TreatmentmightbeconsideredforthosewhoarepositiveforLTBI.
Positive TST for LTBI
Positive TST Reaction Types of Individual≥5mm •HIV-infectedpersons
•Organtransplantrecipients•Personswhoareimmunosuppressedforotherreasons
≥15mm •IndividualsfromcountrieswithlowincidenceofTB≥10mm •Closecontacts
•Recentimmigrants•Injectingdrugusers•Residents&employeesofhighriskcongregatesettings(suchascorrectionalfacilities,nursinghomes,homelessshelters,hospitals&otherhealthcarefacilities)
•PersonswithfibroticchangesonCXR
TB IN CHILDREN• Recommendedtreatmentregimens&dosagesforTBinchildrenareasthefollowing:-
TB casesRegimen
Intensive phase Maintenance phase•NewsmearpositiveornegativePTB•LesssevereEPTB 2HRZ 4HR
•SevereconcomitantHIVdisease 2HRZE 4HR•SevereformofEPTB•TBmeningitis/spine/bone 2HRZE 10HR
•PreviouslytreatedsmearpositivePTBincluding relapse & treatment afterinterruption
3HRZE 5HRE
Drug Dose (range) in mg/kg Maximum doseIsoniazid* 10(10-15) 300mgRifampicin 15(10-20) 600mgPyrazinamide 35(30-40) 2gEthambutol 20(15-25) 1g*Pyridoxine5-10mgdailyneedstobeaddedifisoniazidisprescribed.• For asymptomatic children with history of TB contact, CXR & TST should be
performed.• Treatment for LTBI in children is either daily 6months of isoniazid or daily 3
monthsofisoniazid+rifampicin
TB IN PREGNANCY, LACTATION & USE OF ORAL CONTRACEPTIVE• First-lineantiTBdrugsexceptstreptomycinaresafeforpregnancy&breastfeeding.• DeferBCGatbirthfornewbornsofmotherswithactiveTB<2monthsbeforedelivery.• Patientsonrifampicinshoulduseanalternativecontraceptivemethodotherthan
oralcontraceptivepills.
Management of Tuberculosis (Third Edition)
5
TB-HIV CO-INFECTION• Isoniazidprophylaxistherapyfor6monthsshouldbeofferedtoallHIVpatients
afteractive TB is ruled out.• Highly Active Antiretroviral Therapy (HAART) during TB treatment reduces
mortality&resultsinearliersputumsmear/cultureconversion.
CD4 count (cells/µl) Timing of HAART initiation
<50 2weeksafterstartingintensivephaseofantiTBtreatment
>50 AftercompletionofintensivephaseofantiTBtreatment
>350 ContinueantiTBtreatment&monitorCD4.CommenceHAARTifCD4drops<350cells/µl.
• Efavirenz is the preferred Non-Nucleoside Reverse Transcriptase Inhibitor(NNRTI) incombinationwith2NucleosideReverseTranscriptase Inhibitors forHIV-TBco-infection.
• ImmuneReconstitution Inflammatory Syndrome (IRIS) usually occurs within 3monthsofantiTBtreatment,typicallywithin2-12weeksafterstartingHAART:o EspeciallyinpatientswithCD4<50cells/µl,anaemiaorEPTBo Majormanifestationsarefeverorlymphadenitis
• Co-trimoxazoleprophylaxisshouldbegivenforTB-HIVco-infection&throughoutantiTBtreatment.
FLOW CHART FOR THE RECOMMENDED 6-MONTHS TREATMENT OF PTB
Visit Duration Regimen Investigations1.
2.
3.
4.
5.
Startoftreatment
2-4weeks
2months
4months
6months
HR
HR
Completionof6monthstreatment
H3R3
H3R3
EHRZ/SHRZ
EHRZ/SHRZ
FBC,RBS,RP,LFT,HIVSputumAFBdirectsmearSputumMTBC&S,CXR
LFTifnecessarySputumAFBdirectsmear*SputumMTBC&Sifsmearremainspositive,CXR
LFT
SputumAFBdirectsmear&CXRonlyifthereisnoclinicalimprovement
SputumAFBdirectsmearCXR
Patients with initial sputum smear negative should have repeat sputum smear at 2monthsofantiTBtreatment.Ifstillnegative,nofurthersputumsampleisrequired.*IfsmearAFBremainspositiveat2months,refertospecialistswithexperienceinTBmanagement,&repeatsputumAFB&sputumMTBC&Sat3months.H3R3=thriceweeklyofisoniazid&rifampicin
E-Ethambutol FBC-Fullbloodcount,RBS-RandombloodsugarH-Isoniazid RP-Renalprofile,CXR-Chestx-rayR-Rifampicin LFT-LiverfunctionTest,HIV-HIVscreeningtestZ-Pyrazinamide MTBC&S-Mycobacterium tuberculosisculture&sensitivity
• Follow-upmaynotbeconductedroutinelyaftercompletionofantiTBtreatment.Patientsshouldbewell-informedonsymptomsofTBrecurrence.
Management of Tuberculosis (Third Edition)
6
FIR
ST-L
INE
AN
TITB
MED
ICAT
ION
S: C
OM
MO
N S
IDE
EFFE
CTS
, DR
UG
-DR
UG
INTE
RA
CTI
ON
S &
HA
AR
T C
ON
CER
N
Dru
gC
omm
on S
ide
Effe
cts
Dru
g-D
rug
Inte
ract
ions
Ant
iTB
& H
AA
RT
Con
cern
Isoniazid
Skin
rash,
jaundice,
hepatitis,
drow
siness,
anorexia,
nausea,
abdominalpain,burning,n
umbnessor
tinglingsensationinthehandsorfeet
•R
eductioninphenytoin&diazepamlevel
•Increaseinthe
toxicityofanticonvulsa
nts,
benzodiazepines,
paracetamol,
serotonergic
antidepressants,w
arfarin&theophylline
Careis
neededw
hentakin
gitwithH
AART
medica
tionsthatcan
cause
peripheral
neuropathy,particularlystavudine
(d4T)&
didanosin
e(ddI)
Rifampicin
Skinrash,jaundice
,hepatitis,anorexia
,nausea,abdominalpain,orangeor
redurine&flusyndrom
e(fever,chills,
malaise,headache,bonepain)
Reductioninplasm
alevelofanti-infectives,hormone
therapy
(inclu
dingethinylestradiol,norethindrone,
tamoxifen,levothyroxine),
methadone,
warfarin,
cyclo
sporine,
corticosteroid,
anticonvulsa
nts,
cardiovascularagents,theophylline,sulfonylurea,
HMG-CoAreductase
inhibitors,
antipsychotics,
benzodiazepines&possiblere
ductioninefficacyof
azoleantifungaldrug
Reduceslevelsofproteaseinhibitors&NNRT
Is
Pyrazin
amide
Skinrash,jaundice
,hepatitis,anorexia
,nausea,abdom
inalpain&jointpain
Excretionmaybeblockedbyprobenecid
Shouldbetaken2hoursbeforedidanosine
(ddI)
Ethambutol
Visualim
pairm
ent
Absorption
delayed
orreduced
byalum
inium
hydroxide
-
Streptom
ycin
Skinrash,
deafness(no
waxon
otoscopy),
dizziness
(vertigo
&nystagmus),decreasedurineoutput
Mayincreaseototoxicity&nephrotoxicitywhenuse
witham
inoglycoside,am
photericinB
,cephalosporins,
cyclo
sporin,cisp
latin,frusemide&vancom
ycin
-
Management of Tuberculosis (Third Edition)
7
ALG
OR
ITH
M O
N M
AN
AG
EMEN
T O
F C
HIL
DR
EN W
ITH
PO
SITI
VE H
ISTO
RY O
F C
ON
TAC
T W
ITH
TB
Note:
•Mantouxtestmaybenegativeinchildrenwhoaremalnourishedandimmunocom
prom
ised.
•Contacttracingandinvestigationsinchildrenaretobedonew
ithin
6 w
eeksofdiagnosisoftheindexpatient.
Management of Tuberculosis (Third Edition)
8
PTB Close Contact*
Symptomatic
Asymptomatic
Mantoux test
10 mm <10 mm
CXR Discharge with advice**
Normal – manage as LTBI
Abnormal – evaluate for active TB
Evaluate for active TB • CXR • Sputum AFB • Mantoux test
(optional)
"
Diagnosis confirmed – treat
Diagnosis inconclusive – refer specialist
ALGORITHM ON INVESTIGATIONS FOR TB CONTACT TRACING IN ADULTS
*Immunocompetentclosecontacts**ToseekmedicaladviceifpatienthassymptomssuggestiveofTBsuchasfever,coughetc.formorethan2weeks.
• ThefollowingconditionsshouldbereferredtospecialistswithexperienceinTBmanagement:-o UnsureofTBdiagnosiso RetreatmentofTBo AdverseeventsfollowingantiTBdrugso MDR-TB&extensivelydrug-resistantTBo EPTBexceptfortuberculouslymphadenitiso Renal&/orliverimpairmentwithTBo HIV-TBco-infectiono SmearnegativeTBo Smearpositiveafter2monthsoftreatmento AllchildrendiagnosedwithTBo MaternalTBo ComplexTBcasesrequiringsurgicalintervention
REFERRAL CRITERIA
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