NATIONAL GUIDELINES ON MANAGEMENT OF TUBERCULOSIS IN CHILDREN
NATIONAL TUBERCULOSIS, LEPROSY AND LUNG DISEASE PROGRAM
Third Edition: August 2017©2017 National Tuberculosis, Leprosy and Lung Disease Program
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LIST OF CONTENTSList of Tables .............................................................................................ivList of Figures ........................................................................................... vList of Abbreviations .................................................................................viForeword .................................................................................................viiAcknowledgement .................................................................................viii
CHAPTER 1 ............................................................................................... 1 1.1Aetiology ......................................................................................... 1 1.2Transmission .................................................................................... 1 1.3PathogenesisofTB .......................................................................... 3 1.4Definitions ....................................................................................... 5
1.5ClassificationofTB ........................................................................... 5
Chapter 2 ................................................................................................. 9 2.1EpidemiologyofTBinchildren ........................................................ 9 2.2TuberculosisControlStrategies ..................................................... 10 2.3RationaleforthePaediatricTBguideline ...................................... 12
Chapter 3 ............................................................................................... 13 3.1DiagnosisofpulmonaryTB ............................................................ 13 3.2DiagnosisofExtraPulmonaryTuberculosis(EPTB) ........................ 15 3.3Investigations ................................................................................. 17 3.4IntracranialTuberculosis ................................................................ 34
Chapter 4 ............................................................................................... 36 4.1StandardOperatingProceduresforinitiatinganti-TBTreatment ..36 4.2RecommendedTreatmentRegimen .............................................. 37 4.3AdditionalManagementDecisions ................................................ 42 4.4Follow-upofaChildonanti-TBTherapy ....................................... 43 4.5PoorResponsetoTreatment ......................................................... 43 4.6TreatmentInterruptions ................................................................ 45 4.7AdversedrugreactionsofantiTBdrugsinchildren ...................... 45 4.8ManagingDrugToxicities ............................................................... 46 4.9TreatmentoutcomesforchildrenontreatmentforTB ................. 47
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Chapter 5 ............................................................................................... 49 5.1DiagnosisofTBinHIV .................................................................... 50 5.2DiagnosisofHIVinTB .................................................................... 51 5.3DifferentialDiagnosisinaHIVinfectedChildwithChronic
RespiratorySymptoms ........................................................................ 52 5.4TreatmentoftheTB/HIVco-infectedchild .................................... 53 5.5AntiretroviralTherapyinHIVInfectedChildwithTB ..................... 58 5.6CotrimoxazolePreventiveTherapy(CPT) ...................................... 63 5.7Immunere-constitutioninflammatorysyndrome(IRIS) ................ 64 5.8PreventionofTBinHIV ................................................................. 64 5.9IPTinHIVinfectedchildren ........................................................... 65
Chapter 6 ............................................................................................... 66 6.1ManagementofababyborntoaMotherwithPTB ...................... 66 6.2Managementoftheasymptomaticneonateexposedto maternalTB ......................................................................................... 67 6.3ManagementoftheneonatewithTBdisease .............................. 67 6.4TBamongchildrenincongregatesettings ..................................... 67 6.5TB/DMco-morbidity ...................................................................... 68 6.6TBamongstreetfamilies ............................................................... 70
Chapter 7 ............................................................................................... 71 7.1ClassificationofdrugresistantTB.................................................. 71 7.2Diagnosis ....................................................................................... 72 7.3TreatmentofDRTBinchildren ..................................................... 73 7.4ExtensiveDrugresistantTB(XDRTB) ............................................ 75 7.5FollowupforDRTBtreatment ...................................................... 76 7.6Sideeffectsforsecond-linetreatmentandmanagement ............. 77
Chapter 8: .............................................................................................. 79 8.1Infectionpreventionandcontrol ................................................... 79 8.2ScreeningforChildContactsofknownTBCases ........................... 82 8.3IPTinHIVinfectedchildren ........................................................... 85 8.4BCGVaccinationinChildren .......................................................... 87
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Chapter 9 ............................................................................................... 88 9.1Family/Householdmembers ........................................................ 89 9.2Thecommunity: ............................................................................ 90 9.3CommunityHealthVolunteers(CHVs)/CommunityHealth
ExtensionWorker(CHEW) ................................................................... 90
Chapter 10 ............................................................................................. 92 10.1Monitoring................................................................................... 92 10.2Evaluation .................................................................................... 93 10.3Qualityrecordsandreports ......................................................... 94
Chapter 11: ............................................................................................ 96 11.1NutritionalAssessment,CounselingandSupport(NACS) process ................................................................................................ 97 11.2Classifyingnutritionstatususingweightforage ......................... 99 11.3Nutritioncareprocess ............................................................... 100
Chapter 12 ............................................................................................102 12.1Pharmaceuticalmanagement.................................................... 102 12.2Quantificationofanti-tuberculosismedicines .......................... 103 12.4Rationaluseofanti-tuberculosismedicines .............................. 106 12.5Pharmacovigilance .................................................................... 108
Annex 1:TuberculinSkinTest ..................................................................... 109Annex 2:StepsforPatientManagementtopreventtransmissionof TBinCommunityandhealthcaresettings ........................................ 115Annex 3:TakingAnthropometricMeasurements ...................................... 116Annex 4:Growthmonitoringcharts ........................................................... 119
Listofcontributors ..................................................................................... 137
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LIST OF TABLESTable1:ClassificationofTB ............................................................................ 7Table2:TypesofEPTBandtheirpresentation ............................................. 16Table3:InvestigationsforTBdiagnosis ........................................................ 17Table4:Adjuncttestforuseinselectedsituations ...................................... 18Table5:Spotandmorningsputumcollectionstrategy ................................ 25Table6:Differentialdiagnosisforchildwithchroniccough/Respiratory
symptoms ............................................................................................ 31Table7:DiagnosisofExtra-pulmonaryTBinchildren ................................... 33Table8:Dosageofindividualanti-TBdrugsaccordingtobodyweight ........37Table9:WHOrecommendedTBtreatmentregimen ................................... 38Table10:Dosagesforachildweighingupto3.9kg ..................................... 39Table11:Dosagesforachildweighing4-25kg ............................................ 40Table12:Dosagesforachildweighing25kgsandabove(adultformulation
dosagetable) ....................................................................................... 40Table13:Pyridoxine(vitaminB6)dosingforchildrenonTBtreatment .......41Table14:FollowupofachildonTBtreatment ............................................ 43Table15:Otherimportantadverseeffects ................................................... 45Table16:TreatmentOutcomesforDrugSensitiveTBPatients .................... 48Table17:PaediatricIntensifiedCaseFindingScreeningTool ....................... 50Table18:AdolescentandAdultIntensifiedCaseFindingScreeningTool .....51Table19:DifferentialdiagnosisofchronicrespiratorysymptomsinHIV
infectedchildren .................................................................................. 52Table20:BaselineLaboratoryInvestigationsforPLHIV ................................ 55Table21:PreferredARTRegimensforTB/HIVCo-infectionforChildren
NewlyInitiating1stLineART ............................................................... 60Table22:PreferredARTRegimensforTB/HIVCo-infectionforPatients
Currentlyon1stLineART1,2 ............................................................. 61Table23:AbbreviationsandNamesofAntiretroviralDrugs ........................ 62Table24:Efavirenzdosageinchildren .......................................................... 62Table25:RitonavirDosingforSuper-BoostingLPV/rinChildrenTaking
Rifampicin ............................................................................................ 63Table26:RecommendeddosesforCotrimoxazole ...................................... 64Table28:SignsandsymptomsofneonatalTB ............................................. 66Table29:ClassificationofdrugresistantTB ................................................. 71Table30:Patternsofdrugresistanceandrecommendedtreatment ...........74Table31:Second-lineanti-TBdrugsfortreatmentofMDR*-TBinchildren 75Table32:PatientmonitoringscheduleforpatientswithMDRTB................ 76
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Table33:Commonsideeffectsofsecond-linemedicines,theirlikelycausingagents,andsuggestedmanagementstrategies .................................. 78
Table34:DoseofIsoniazid(INH)forIsoniazidPreventiveTherapy(IPT)inchildren ............................................................................................... 86
Table35:Rolesofthedifferenthealthfacilities ........................................... 91Table36:Dimensionsofdataquality ........................................................... 94Table37:TBRecordingandreportingtools ................................................. 95Table38:Anthropometriccriteriatoidentifysevere,moderateandatrisk
categoriesofacutemalnutritionforchildrenandadolescents* .........98Table39:MUACcriteriatoidentifymalnutritionofchildrenlessthan5years
inthecommunity ................................................................................ 99Table40:Triagetodeterminetreatmentofmalnutrition .......................... 100Table41:Stepsinthenutritioncareprocess ............................................. 101Table42:Typesofinventoryrecords .......................................................... 104
LIST OF FIGURESFigure1:TransmissionofTBfromanadulttoachild .................................... 2Figure2:TheWorld’s30HighBurdenCountries ........................................... 9Figure3:TheEndTBStrategy ....................................................................... 11Figure4:XpertMTB/Rifalgorithm ................................................................ 19Figure5:PicturessuggestiveofPulmonaryTB ............................................. 27Figure6:X-rayssuggestiveofextrapulmonaryTB ........................................ 28Figure7:ManagementofHIVinachildwithTB .......................................... 57Figure8:DiagnosticalgorithmforthediagnosisofDR-TBinchildrena .......73Figure9:ManagementofaChildwhohasbeenexposedtoanadolescentor
adultwithPulmonaryTB ..................................................................... 85Figure10:Thepharmaceuticalmanagementcycle .................................... 102Figure11:FlowoflogisticManagementInformation ................................ 105Figure12:Themedicineusecycle .............................................................. 107Figure13:Administrationofthetuberculinskintest ................................. 113Figure14:Readingthetuberculinskintest ................................................ 114
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LIST OF ABBREVIATIONS
3TC LamivudineABC AbacavirAZT ZidovudineCHEW Community Health Extension WorkerCHW Community Health WorkerCm CapreomycinCPT Cotrimoxazole Preventive TherapyCs CycloserineCSF Cerebrospinal FluidEFV EfavirenzEPTB Extra Pulmonary TBESR Erythrocyte Sedimentation RateFNA Fine Needle AspirateHAART Highly Active Antiretroviral TherapyIGRA Interferon-Gamma Release AssayINH IsoniazidIRIS Immune Reconstitution SyndromeLfx LevofloxacinLPV/r Lopinavir/Ritonavir(Kaletra)MAM Moderate Acute MalnutritionMTB Multidrug Resistant TBMUAC Mid Upper Arm CircumferenceNaCl Sodium ChlorideNVP NevirapinePCP Pneumocystis Jirovenci PneumoniaPto ProthionamideRIF RifampicinRTV RitonavirSAM Severe Acute MalnutritionTB TuberculosisTBM TB MeningitisTST Tuberculin Skin TestTU Tuberculin UnitsW/H Weight for HeightW/L Weight for LengthWHO World Health OrganizationXDR-TB Extensively Resistant TuberculosisXpert MTB/RIF Gene Xpert TestZN Ziehl Neelsen
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FOREWORD
The National Tuberculosis, Leprosy and Lung Disease Program (NTLD-Program) is mandated to develop policies, build capacity and provide technical assistance in health to the devolved county system.
Treatment of tuberculosis has over the years focused more on adults leaving children with little attention as medical practitioners considered children to be of little epidemiologic significance. Available data indicates that about 9% of TB cases notified in Kenya are children below 15 years. This is thought to be an underestimate yet TB causes significant morbidity and mortality in children. Tuberculosis in children is also an important indicator of on-going TB transmission in the society.
Medication for treating TB in children has evolved over the years with the current regimen now containing Ethambutol that was not previously used in children. The actual formulations have been reviewed to cater for higher doses of Isoniazid and Rifampicin used in children below 25kg body weight. These newer formulations enable treatment with a regimen that has a pleasant taste and is simpler for the health care workers and the caregivers to administer. This enhances treatment adherence and leads to improved treatment outcomes for children with TB.
With the high burden of TB in the population, there is need to ensure contact tracing for all child contacts of bacteriologically diagnosed TB. Contacts found to have TB disease are treated. Those below the age of five years without the disease are initiated on Isoniazid prophylaxis to protect them from developing TB.
Children with TB and HIV co-infection require management for both conditions to reduce their morbidity and mortality rates. This should be carefully planned to minimize drug interactions, development of drug resistance and ensure good treatment outcomes.
This guideline seeks to provide guidance to the health care workers on the management of TB in children. It seeks to demystify TB diagnosis in children especially in the context of new diagnostic methods expected to revolutionize TB diagnosis and management. It also guides health care workers on the treatment of TB in children and the management of child TB contacts. This guideline will also act as a reference material for medical students, researchers and the entire community.
Dr. Kioko Jackson K., OGWDIRECTOR OF MEDICAL SERVICES MINISTRY OF HEALTH
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ACKNOWLEDGEMENT
The National Tuberculosis, Leprosy and Lung Disease Program is indebted to the Ministry of Health’s leadership and health care workers in the implementation of TB control activities in the country and their support during the revision of this guideline.
The NTLD-Program specifically acknowledges the input received from the following technical and training institutes:Ministry of HealthWorld Health Organization (WHO)US Centers for Disease Control and Prevention (CDC)United States Agency for International Development (USAID)National Tuberculosis, Leprosy and Lung Disease Program (NTLD-Program)National AIDS and STI Council (NASCOP)University of Nairobi (UON)Kenya Medical Research Institute (KEMRI)Moi Teaching and Referral Hospital (MTRH)International Center for AIDS Care and Treatment Program (ICAP)Centre for Health Solutions - Kenya (CHS)
Dr. Maureen KameneHEAD OF NATIONAL TUBERCULOSIS, LEPROSY AND LUNG DISEASE PROGRAM MINISTRY OF HEALTH
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CHAPTER 1
INTRODUCTION TO TUBERCULOSIS
1.1 Aetiology
TBiscausedbythebacteriumMycobacterium tuberculosis(M. tuberculosis).M. tuberculosis and seven very closely related mycobacterial species (M. bovis, M. africanum, M. microti, M. caprae, M. pinnipedii, M. canetti and M. mungi) together comprisewhat is knownas theM. tuberculosis complex.Most, but not all, of these species have been found to cause diseases inhumans. M. tuberculosisorganismsarealsocalledtuberclebacilli.
Inraresituations,Non-TuberculousMycobacteria(NTM)maycauseadiseasesimilartotypicalTB.
1.2 Transmission
M. tuberculosis is transmitted through airborne infectious droplet nucleiwhich are generated when persons who have pulmonary or laryngeal TBdiseasecough,sneeze,shout,orsing.Thesetinyparticles(1–5micronsindiameter)canremainsuspendedintheairforseveralhours.M.tuberculosisis transmittedthrough theair,notbysurfacecontact.Transmissionoccurswhen a person inhales droplet nuclei containingM. tuberculosis, and thedropletnucleitraversethemouthornasalpassages,upperrespiratorytract,andbronchitoreachthealveoliofthelungs.
Tobe infectedwith the tuberclebacillus apersonmustbeexposed to aninfectiouscaseofTB.
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Figure 1: Transmission of TB from an adult to a child
Risk factors of exposure to the TB bacillusa) IncidenceofinfectiousTBinpopulation/communityb) Averagedurationofinfectiousnessofcasesc) Numberofcases/contactinteractionsovertimed) Populationdensitye) Familysizef) Povertyg) Overcrowding
Risk factors for transmission1. Level of TB infection in a person:ApersonwithTBwhoexpelsmore
bacilliismoreinfectiousthanonewhoexpelsfewerbacilli.Thelevelof infection is increased if the patient has a cough or pulmonarydisease, poor coughetiquette, inappropriate treatment, cavitatorydisease,cultureorbacteriologicallypositivedisease.
2. Susceptibility of the exposed child with the contact: This is dependentontheimmunestatusoftheexposedchild. Ifthechildcontact has aweakened immune system, TB transmission ismorelikely.Theveryyounghaveahigherriskofdevelopingdiseaseuponexposure.
3. Environmental factors: These are factors that may increase theconcentration of the bacilli in the immediate environment of thechild. They include the concentration of infectious droplet nucleiin the air, exposure in small-enclosed spaces, recirculation of aircontaining infectious droplet nuclei, improper specimen handlingproceduresthatgenerateinfectiousdropletnuclei.
4. Proximity, frequency and duration of exposure with the infectious person:Thelongerthedurationofcontact,themorefrequentthecontact,thecloserthecontact,thehighertheriskoftransmission.
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1.3 Pathogenesis of TB
Upon exposure to an infectious case, the child inhales droplet nucleicontaining infectious bacilli and they reach the alveoli. They are ingestedby alveolar macrophages which destroy them. A few bacilli may survive,multiply inthemacrophagesandarereleasedwhenthemacrophagesdie.Thisprocessinducesanimmuneresponse.
The immune cells in the alveoli may form an immune capsule called agranuloma(Ghonfocus)thatkeepsthebacillicontainedandundercontrol.Itmightalsoinvolvethedraininglymphnodes.BoththegranulomaandthedraininglymphnodesarecalledGhoncomplex(Primarycomplex).Ifthisispresentwithoutsignsandsymptomsofdisease,itislatent TB infection.
If the immunesystemcannotkeep thebacilliundercontrol, theymultiplyrapidly, affecting the lung parenchyma and the airways. Theymay spreadthrough the lymphatics or the blood stream to the rest of the body. ThechildwillthenbesymptomaticandsaidtobehavingTBdisease(primary TB disease).
Withouttreatment,manychildreninfectedwithM.tuberculosiswilldevelopTBdisease in thefirst or second year after infection. In others, thebacilliremaindormantforalongtimeandtheymaydevelopTBdiseaseatsomepoint in their lifetime. Progression of the latent infection to disease issecondary TB disease.
Risk of latent TB infection progressing to TB disease
Children with latent TB infection can progress to active TB disease. Riskfactorsforthisprogressioninclude:
• HIVinfection• Ageespeciallythoseundertheageoftwoyears• RecentinfectionwithM.tuberculosis(withinthelasttwoyears)• HistoryofpreviouslypoorlytreatedTB• Immunosuppressivetherapy• Other immune suppressive conditions e.g. diabetes, silicosis,
malignancies
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Progressionof theprimary complexmay lead toenlargementofhilarandmediastinal nodes with resultant bronchial collapse. Progressive primaryTB diseasemay developwhen the primary focus cavitates and organismsspreadthroughcontiguousbronchi.Lympho-haematogenousdissemination,especiallyinchildren,mayleadtomilliaryTBwhencaseousmaterialreachesthebloodstreamfromaprimaryfocusoracaseatingmetastaticfocusinthewall of a pulmonary vein. TBmeningitismay result from haematogenousdissemination.
Bacillimayremaindormantinthelungsforseveralmonthsoryears.Apositivetuberculinskintest(TST)orInterferonGammaReleaseAssay(IGRA)whereavailablewouldbetheonlyevidenceofinfection.
TB in young children is often disseminated and rapidly progressive
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1.4 Definitions
TB infectioniswhenapersoncarriesthemycobacteriumtuberculosisbacteriainsidethebody.ManypeoplehaveTBinfectionandseemtobehealthy.ApositiveTSTindicatesaninfection-butanegativeTSTdoesnotexcludethepossibilityofinfection.TBinfectionisalsocalledlatentTB.
TB diseaseoccursinsomeonewithTBinfectionwhenthebacteriainsidethebodystarttomultiplyandbecomenumerousenoughtodamageoneormoreorgansofthebody.Thisdamagecausesclinicalsymptomsandsignsandisreferredtoas“Tuberculosis”oractivedisease.
Index case (index patient): TheinitiallyidentifiedcaseofneworrecurrentTB,inapersonofanyage,inaspecifichouseholdorothercomparablesettinginwhichothersmayhavebeenexposed.Anindexcaseisthecasearoundwhichacontactinvestigationiscentred(butisnotnecessarilythesourcecase)
Household contact: Apersonwhosharedthesameenclosedlivingspaceforoneormorenightsorforfrequentorextendedperiodsduringthedaywiththe indexcaseduringthe3monthsbeforecommencementof thecurrenttreatmentepisode
Close contact: Apersonwhoisnotinthehouseholdbutsharedanenclosedspace, such as a social gathering,workplace or facility, for extended timeperiods during the day with the index case during the 3 months beforecommencement of the current treatment episode (e.g. care taker, schoolstaff)
Childrenreferstothosebetween0to14yearsofage
Infant isachildoflessthan1yearofage(0-12monthagegroup)
1.5 Classification of TB
A presumptive TB case isonewhopresentswithsymptomsorsignssuggestiveofTB(previouslyknownasaTBsuspect).
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Case definitions
a) A bacteriologically confirmed TB case: one from whom a biologicalspecimen is positive by smear microscopy, culture or WRD (WHO-approvedrapiddiagnosticssuchasXpertMTB/RIF).AllsuchcasesshouldbenotifiedregardlessofwhetherTBtreatmentwasstartedornot.
b) A clinically diagnosed TB case: AclinicallydiagnosedTBcaseisonewhodoesnotfulfilthecriteriaforbacteriologicalconfirmationbuthasbeendiagnosed with active TB by a clinician or other medical practitionerwhohasdecidedtogivethepatientafullcourseofTBtreatment.Thisdefinition includes cases diagnosed based on X-ray abnormalities orsuggestive histology and extra pulmonary cases without laboratoryconfirmation. Clinically diagnosed cases subsequently found to bebacteriologicallypositive(beforeorafterstartingtreatment)shouldbereclassifiedasbacteriologicallyconfirmed.
Bacteriologically confirmed or clinically diagnosed cases of TB are alsoclassifiedaccordingto:
• Anatomicalsiteofdisease• Historyofprevioustreatment• Drugresistance• HIVstatus
ThisisshowninTable 1.
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Table 1: Classification of TB
Classification based on anatomical sites
Pulmonary TB (PTB)ThisisTBdiseaseinvolvingthelungparenchyma(segmentalorlobarconsolidation,TBbronchopneumonia).MilliaryTBisdisseminateddiseasebutclassifiedasPTBbecausetherearelesionsinthelungs.
Extra pulmonary TB (EPTB)
ThisisTBdiseasepresentoutsidethelungparenchyma.• Intra-thoracic(Insidethechest,butoutsidethelungtissue):pleuraleffusion,intra-
thoraciclymphadenopathy,(mediastinal,paratrachealorhilarlymphadenopathy)• Extra-thoracic(Outsidethechest):PeripheralLymphnodes,abdomen,
genitourinarytract,skin,jointsandbones,meninges.
ApatientwithbothpulmonaryandextrapulmonaryTBshouldbeclassifiedasacaseofPTB.
Classification based on history of previous TB treatment (patient registration group)
New patients PatientwhohasneverbeentreatedforTBorhastakenanti-TBdrugsforlessthanonemonth.
Previously treated patients
Patientwhohasreceived1monthormoreofanti-TBdrugsinthepast.Theyarefurtherclassifiedbytheoutcomeoftheirmostrecentcourseoftreatmentasfollows:
• Relapse patients:previouslytreatedforTB,declaredcuredortreatmentcompletedattheendoftheirmostrecentcourseoftreatmentandarenowdiagnosedwitharecurrentepisodeofTB
• Treatment after failure patients:previouslytreatedforTBandwhosetreatmentfailedduringtheirmostrecentcourseoftreatment
• Treatment after loss to follow-up patients:previouslytreatedforTB,anddeclaredlosttofollow-upduringtheirmostrecentcourseoftreatment.(Thesewerepreviouslyknownasreturnafterdefaultpatients)
Patients with unknown previous TB treatment historydonotfitintoanyofthecategorieslistedabove
Classification of TB patients based on HIV status
HIV-positive TBpatientwhohasapositiveresultfromHIVtestingconductedatthetimeofTBdiagnosisorotherdocumentedevidenceofHIVdiagnosis.
HIV-negativeTBpatientwhohasanegativeresultfromHIVtestingconductedatthetimeofTBdiagnosis.AnyHIV-negativeTBpatientsubsequentlyfoundtobeHIV-positiveshouldbereclassifiedaccordingly.
Unknown HIV statusTBpatientwhohasnoHIVtestresultandnootherdocumentedevidenceofHIVdiagnosis.Ifthepatient’sHIVstatusissubsequentlydetermined,heorsheshouldbereclassifiedaccordingly.
Classification based on drug resistance according to Drug Susceptibility Testing
Monoresistance Resistancetoanyone ofthefirst-lineanti-TBdrugs.
Polydrug resistance Resistancetomorethanonefirst-lineanti-TBdrug(other than both Isoniazid and Rifampicin).
Multidrug resistance Resistancetoboth Isoniazid and Rifampicin ± anyotherfirst-lineanti-TBdrugs
Extensive drug resistance
Resistancetoany fluoroquinolone (Levofloxacin,Moxifloxacin)andtoat least one of three second-line injectable drugs(Capreomycin,KanamycinandAmikacin),inadditiontomultidrugresistance
Rifampicin resistance
Resistance to Rifampicindetectedusingphenotypicorgenotypicmethods,withorwithoutresistancetootheranti-TBdrugs.Itincludesanyresistancetorifampicin,whethermonoresistance,multidrugresistance,polydrugresistanceorextensivedrugresistance
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Please note:
1. AllTBpatientsmustbetestedforHIV,andalleffortsmustbemadetoclassifythemeitherasHIVpositiveorHIVnegativeasthisimpactsmanagement.
2. Theabovecategoriesofclassificationbasedondrugresistancearenot allmutually exclusive.When enumerating Rifampicin-resistantTB (RR-TB), for instance, multidrug-resistant TB (MDR-TB) andextensivelydrug-resistantTB(XDR-TB)arealsoincluded.
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CHAPTER 2
Background
2.1 Epidemiology of TB in children
It is estimated that one third of the world’s population is infected withMycobacteriumtuberculosis.In2015,itisestimatedthat10.4milliongloballypeoplefellillwithTB,ofwhomabout1.8milliondied.OftheannualTBcases,about10%occurinchildren(under15yearsofage).Kenyaisamongthe30TBhighburdencountriesintheworldandisamongthe14withhighburdenforTB,TB/HIVandMDR-TBasseeninFigure2.ThislistwillbeusedbyWHObetween2016and2020.
Figure 2: The World’s 30 High Burden Countries
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In2015,Kenyareportedatotalof81,518casesofallformsofTB,ofwhom8.5% were Children aged less than 15 years. This is a decline from 9.5%notifiedthepreviousyear.Inthelast5years,KenyahasreportedadeclineinthenumberofreportedTBcasesatarateof1%annuallypossiblyduetoeffectivecontrolinterventionscoupledwiththedecliningHIVprevalenceinthepopulation.
2.2 Tuberculosis Control Strategies
The End TB Strategy The previous STOP TB Strategy that ended in 2015 had various notableachievements. Among thesewas 37million lives saved between the year2000and2013througheffectiveTBdiagnosisandtreatment,a45%declineinTBmortalityrateanda41%declineinTBprevalenceratesince1990.Inaddition,HIVrelatedTBdeathsreducedby34%inthelastdecadewithtriplethenumberofDRTBcasesdiagnosedandathree-foldincreaseintreatmentcoveragesince2009.However,therewerechallenges:3millionpeoplewithTBweremissedbythehealthsystemseveryyear,TB/HIVinterventionsstillneeded further scalingupandawideninggapbetweenpeoplediagnosedwithMDR-TBandthoseputontreatmentwerenoted.ThiscouldcompromisethegainsmadeinMDRTBmanagement.
Intheinterestofsocialjusticeanduniversalhealthcoverage,everyonewithTBshouldhaveaccesstotoolsandservicesforrapiddiagnosis,treatmentandcare,whichisthecornerstoneoftheendTBStrategyasoutlinedinFigure3.
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Figure 3: The End TB Strategy
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Global priority indicators and targets for monitoring the implementation of the End TB Strategy
Thefollowingindicatorswereoutlinedandallcountriesshouldaimtoreachthesetargetsby2025.
• Treatment coverage:NumberofpeoplethatdevelopedTB,andwerenotifiedandtreated,outofthetotalestimatednumberofincidentcasesinthesameyear(%):≥ 90%
• TB treatment success rate: Number of TB patients who weresuccessfullytreatedoutofallnotifiedTBcases(%):≥ 90%
• Preventive treatment coverage: Number of people living withHIV and childrenwho are contacts of caseswhowere started onpreventive treatment (IPT) for latent TB infection, out of all thoseeligible(%):≥ 90%
• TB affected households facing catastrophic costs: Number of TBpatients and their households that experienced catastrophic costsduetoTB,outofallTBpatients(%):0%
• Uptake of new diagnostics and new drugs:NumberofTBpatientswhowerediagnosedusingWHO-recommendedrapidtests,outofallTBpatients(%):≥ 90% andnumberofTBpatientswhoweretreatedwithrecommendedregimensincludingnewTBdrugs:outofthoseeligiblefortreatmentwithsuchdrugs(%):≥ 90%
2.3 Rationale for the Paediatric TB guideline
TheseguidelineshavebeendevelopedtoguidethehealthcareworkersonthemanagementofchildrenwithTBandTB/HIV.Theyhavebeenreviewedto incorporate revisions in the treatment regimensandavailabilityofnewformulations for the treatment of TB in children. Advances in diagnosticmethodstoincludenewertestssuchasGeneXpertandtheuseofspecimensotherthansputumhavealsobeenincludedinthisrevisededition.It is expected that these guidelines will go a long way in accelerating TBcasedetectionamongchildren,reducedmortalityandimprovedtreatmentoutcomes.
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CHAPTER 3 Diagnosis of TB in Children
Thediagnosis of TB in children reliesona goodhistory, a careful physicalexaminationaswellastherelevantinvestigations.AlleffortsshouldbemadetogetaspecimenforbacteriologicalconfirmationofTBinchildren.In cases where it is not possible to obtain a specimen in a timely way, this should not be a barrier to making the diagnosis, a presumptive TB diagnosis may be used for treatment decisions.
A trial treatmentwith anti-TB drugs is not recommended as amethodofdiagnosingTBinchildren.MostchildrenwithTBhavePulmonaryTB.However,approximately30–40%ofchildrenwithTBhaveTBinorgansoutsideofthechest–alsocalledextra-pulmonaryTB.
3.1 Diagnosis of pulmonary TB
HistoryThekeyelementsofhistoryare:
a ) H i s t o r y o f contact with an adolescent or adult with confirmed or presumptive TB within the last two years
Close contact is defined as a person who has confirmed or presumptiveTB living inthesamehouseholdor in frequentcontactwiththechild (e.g.caretakers,schoolstaff).
If no index case is identified, always ask about anyone in the household/dormitory/classroom/schooltransportwithchroniccough-ifpresentrequestassessmentofthatpersonforpossibleTB.MostchildrenwhodevelopTB,dosowithintwoyearsofexposure.
b) History of symptoms suggestive of TBThemostcommonsymptomsassociatedwithTBincludethefollowing:
• Progressiveandnon-remittingcough• Feverand/ornightsweats• Lethargy/reducedplayfulness/lessactive• Poorweightgainorweightloss(failuretothrive)
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The diagnosis of TB in children relies on a careful history and physical examination
Physical examination
a) General examinationExaminethechildandcheckfor:
• Temperature>37.5(fever)• Weight(toconfirmpoorweightgain,weightloss)• Respiratoryrate(fastbreathing)
b) Examination of the Respiratory SystemIn early stages of pulmonary TB, the respiratory exam may show fewabnormal signs.As thediseaseprogresses respiratory signs becomemoreobviousasfollows:
• Cough• Increasedrespiratoryrate(fastbreathing)• Respiratorydistresse.g. labouredbreathing, chest in-drawing (this
showsseveredisease)• Percussionnote-dullwhenlobarconsolidationispresent(normal
resonanceinmanychildrenwithPTB)• Auscultationmaybenormalinearlydisease,andabnormalinmore
advanceddisease(crackles,bronchialbreathing)
The classic symptoms of PTB are cough, fever, poor weight gain and lethargy/reduced playfulness
Insomecases,theremaybeless typical clinical presentations of PTB, especiallyinchildrenunderage2years,orwhoareseverelyimmunosuppressed.Inthiscase,thechildmaypresentwithfeaturesof acute severe pneumonia.Acuteseverepneumoniapresentswith:
• Coughofacuteonset(lessthan7days),• Fastbreathing/tachypnoea(age2-12monthsRR>50/min,age1–5
yrRR>40/min)• Signs of respiratory distress such as chest in-drawing, grunting,
hypoxia(oxygensaturation<92%).
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In children under 2 years of age or severely immunosuppressed children(SeveremalnutritionorHIVdisease),TBmaypresentasanacutepneumoniaandtheHCWshouldhaveahighindexofsuspicionfromthefirstpresentation.
3.2 Diagnosis of Extra Pulmonary Tuberculosis (EPTB)
Approximately 30-40% of children with TB have TB in organs outside of the chest – also called extra-pulmonary TB.YoungerchildrenandchildrenwithHIVdiseasearemorelikelytohaveEPTBthanolderchildrenandadults.EPTBdiseaseisTBoutsidethelungparenchyma.Itcanbe:
• Intra-thoracic (inside the chest, but outside of the lung tissue) –pleuraleffusion,intra-thoraciclymphadenopathy(mediastinal,para-trachealorhilarlymphadenopathy)
• Extra-thoracic (outside the chest) – peripheral lymph nodes,abdomen,genitourinarytract,skin,jointsandbones,meninges.
Themost common site for EPTB is in the lymph nodes (hilar or cervical),followedbyTBmeningitis.Frequently,achildwillhaveacombinationofbothpulmonaryandextrapulmonaryTB,withinfectionstartinginthelungsanddisseminatingtootherpartsofthebody.
HistoryForchildrensuspectedtohaveEPTB,twoelementsofhistoryareimportant:
• History contact with an adolescent or adult with confirmed orpresumptiveTBwithinthelasttwoyears
• HistoryofsymptomssuggestiveofEPTBChildrenwithEPTBmayhavetheclassicsymptomssuggestiveofTB:
• Feverand/ornightsweats• Poorweightgainorweightloss• Lethargy,lessactive,reducedplay• Cough
Inaddition,theyhavesymptomsspecifictothesiteofEPTBforexample:• Swollennecklymphnodes,maybedischargingcaseousmaterial• Symptoms of meningitis – progressive unrelenting headache,
irritability, confusion, focal neurologic weakness, convulsions,reducedconsciousness
• Symptoms of hilar lymphadenopathy compressing the airways –Wheeze,rapidbreathingandworseningbreathlessness(mayormaynothavecough)
Table2showssomeofthesitesEPTBmayaffectandthepresentation.
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Table 2: Types of EPTB and their presentation
Site of EPTB History Clinical signs
CervicalLymphadenitis
-Progressiveswellinginneck-Usuallyononeside,butmayoccuronbothsides-Severalswellingsthatarenotpainful+/-thickyellowdischarge
-EnlargedcervicalLN>2cmdiameter-Nothotortender+/-Dischargingsinus(caseousdischarge)-Mostcommoninneckarea
Hilarlymphadenopathy
-Mayormaynothavecough-Noisybreathing(parentmaydescribeasawheeze)-Fastbreathing,progressivebreathlessness
-Tachypnoea-+/-respiratorydistress-Normalpercussionnote-Breathsoundsmaybelouderononesideofchestthantheother-Wheeze/rhonchiwhichareoftenasymmetric,lowpitched,withpoorresponsetobronchodilators
PleuralTB
-Chestpainonaffectedside-Progressivebreathlessness-Mayormaynothavecough
-Dullnessonpercussion-Reducedbreathsoundsonaffectedside
TBmeningitis
-UnremittingheadacheprogressingtoIrritability/abnormalbehaviour-Lethargic/reducedlevelofconsciousness+/-Convulsions
-Irritability/abnormalbehaviour-Lethargic/reducedlevelofconsciousness,+/-Convulsions-Neckstiffness-Bulgingfontanel-Cranialnervepalsies
MilliaryTB-Non-specific-Lethargic+/-Cough
-Fever-Wasting+/-Respiratorysigns+/-Hepatosplenomegaly
AbdominalTB -Painlessabdominalswelling+/-GITdisturbances
-Ascites+/-Hepatosplenomegaly
SpinalTB -Painlessdeformityofspine-Mayhavelowerlimbweakness/paralysis
-Gibbusdeformity-X-rayshowsanteriorvertebralcollapse
PericardialTB-Cardiacfailure:Cough,difficultyinbreathing,swellingoflegsand/orabdomen
-Cracklesinlungs-Apexbeatdifficulttopalpate-Muffledheartsounds
TBboneandjoint(excludingspine)
-Painlessswellingendoflongboneswithlimitationofmovement-Painlessunilateraljointswelling
-Effusionoflargejoints(usuallykneeorhip)-Limitationofmovementinlongbones
The most common form of extra-pulmonary TB in children is lymphadenopathy. This can be cervical or hilar
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3.3 Investigations
Afterhistoryandphysicalexamination,investigateeverychildsuspectedtohaveTB.InvestigationscommonlyusedfordiagnosisofTBareasshownintable 3. These are categorized as bacteriological investigations, radiologicinvestigationsadimmunologicinvestigations.
Table 3: Investigations for TB diagnosisBacteriological investigations*
Laboratory test Target Purpose
MTB/RifGeneXpert
• ThefirstlinetestforallpresumptiveorsuspectedTBinInfants,childrenandadolescents
• SurveillanceforDrugResistantTBamongchildrenpreviouslytreatedforTB,childcontactsofDRTBpatients,refugees,prisoners,childrennotimprovingonfirstlineTBtreatment
FordiagnosisofTB
Todeterminerifampicinsusceptibility
Doneforchildspecimensofsputum,CSF,Gastricaspirate,Nasopharyngealaspirates,Pleuralfluid,Pericardialfluid,Asciticfluid,FNA
Smearmicroscopy(FluorescentandLightmicroscopy)
Infants,childrenandadolescentswithpresumptivePulmonaryTB
OnlyusedinsituationswhereXpertisnotaccessible
Monitoringsmearpositiveand/orgeneXpertpositiveTBpatientsontreatmentatmonths2,5and6
Radiological investigations
X-ray ChestX-rayforallinfants,childrenandadolescentswithpresumptiveTB
X-raysoftheaffectedbone,joint,spineasappropriate
DiagnosisofTBandEPTBinallchildrenwherex-rayservicesareavailable.
ForchildrenobtainAnteroposteriorandlateralCXRviews
Ultrasound AbdominalultrasoundChestultrasound
DiagnosisofabdominalTBDetectionofpleuraleffusion
CTScanorMRIHeadCT,ChestCTasneededMRIoftheabdomen,head,chestorspineas needed
Evaluationofsevereorcomplicatedcases
Immunologic Tests
Tuberculinskintest Children
UsefultesttodetectTBexposureinchildrenandsupportpresumptiveclinicaldiagnosisinsituationswherethereisnoobviouscloseTBcontacttothechild
Interferongammareactionassay(IGRA) Children SimilarroletoTSTbutmoreexpensive.
Whenever possible try to make a bacteriological diagnosis of TB in infants and older children by obtaining specimens and sending them for Gene Xpert (preferred first line test), AFB microscopy or TB culture.
*This includes tests that detect the TB bacillus or its antigens
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Other testsmay be used togetherwith those above to further support adiagnosisofTB.Theseareshownintable4.
Table 4: Adjunct test for use in selected situations
Laboratory Test Target Purpose
Line Probe Assay(LPA)
Childrenwhoare:• MTB positive rifampicin
sensitive, and are at high riskforDRTB
• MTB positive rifampicinresistant, and are either highorlowriskforDRTB
To determine if Isoniazidresistanceispresent
CultureandDST
Childrenwhoare:• Eligible for LPA should also
have a culture and DSTrequested
• Children with clinicallysuspected TB whose Xpert isnegative
• Childrenwhoareontreatmentfor TB who are failing torespondtotherapy
TodiagnoseTB
To determine the drugsensitivitypattern
Todiagnoseinfectionswithnon-tuberculousmycobacteria
Histology All presumptive extra-pulmonaryTBwhereFNAisindeterminant
Tissue diagnosis in suspectedEPTBe.g.TBadenitis
Xpert MTB/Rif AssayThisisamoleculartestusedtodetectpresenceofM. Tuberculosis aswellasRifampicinresistance.ItismoresensitiveandspecificthansputummicroscopyindetectingTB.
It is the preferred test of choice for TB diagnosis among children.The use of Xpert for TB diagnosis in children is as shown in figure 4.
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Figure 4:Xpert MTB/Rif algorithm
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Specimen collection
Bacteriologicaltestsareconductedonaspecimencollectedfromthechild.Themostcommonspecimenusedissputumwhichcanbeobtainedbyaskingthechildtoexpectorate.YoungerchildrenhoweverarenotabletoexpectoratehencetheHCWshoulduseothermeanstoobtainthespecimen.
Other specimen that may be used include CSF, Gastric aspirates,Nasopharyngeal aspirates, Pleural fluid, Ascitic fluid, FNA and Lymphnodebiopsies.
Toensureagoodyieldfromthebacteriologictests,thespecimenshouldbecorrectlycollectedandrelayedtothelabinatimelymanner.
The results should also be relayed to the requesting clinician in a timelymanner.
a) Procedure for expectoration
Background
AllsputumspecimensproducedbychildrenshouldbesentforXpertMTB/Rifandwhereavailable,mycobacterialculture.WhereaccesstoXpertMTB/Rifisnotpossible,thespecimenmaybesubjectedtoAFBmicroscopy.
Childrenwhocanproduceasputumspecimenmaybeinfectious,so,aswithadults,theyshouldbeaskedtoexpectorateoutsideinopen,wellventilatedplacesandnot inenclosedspaces(suchastoilets)unlessthere isa roomspeciallyequippedforthispurpose.
Fordiagnosis,twospecimensatleast4hoursapartarecollected.
Procedure 1. Givethechildconfidencebyexplainingtohimorher(andanyfamily
members)thereasonforsputumcollection.2. Instruct the child to rinse his or her mouth with water before
producing the specimen. This will help to remove food and anycontaminatingbacteriainthemouth.
3. Instructthechildtotaketwodeepbreaths,holdingthebreathfora
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fewsecondsaftereachinhalationandthenexhalingslowly.Askhimor her to breathe in a thirdtime and then forcefully blow the airout.Askhimorhertobreathinagainandthencough.Thisshouldproducesputumfromdeep in the lungs.Ask thechild tohold thesputumcontainerclosetothe lipsandtospit into itgentlyafteraproductivecough.
4. If the amount of sputum is insufficient, encourage the patient tocoughagainuntilasatisfactoryspecimenisobtained.Rememberthatmanypatientscannotproducesputumfromdeepintherespiratorytrackinonlyafewminutes.Givethechildsufficienttimetoproduceanexpectoration,whichheorshefeels,isproducedbyadeepcough.Ifthereisnoexpectoration,considerthecontainerusedanddisposeofitintheappropriatemanner.
b) Procedure for Gastric aspiration
Background
Gastric aspiration is a technique used to collect gastric contents to try toconfirmthediagnosisofTBbyXpertMTB/RifinchildrenwithpresumptivePTBwhocannotexpectorateorsputumcannotbeinducedusinghypertonicsaline.
During sleep, the lung’s mucociliary system beats mucus containingMycobacteriumTBupintothethroat.Themucusisswallowedandremainsin the stomach until the stomach empties. Therefore, the highest yieldspecimensareobtainedfirstthinginthemorning.
Performingthetestproperlyusuallyrequirestwopeople(onedoingthetestandanassistant).Childrennotfastedforatleast4hours(3hoursforinfants)prior to theprocedureand childrenwith a lowplatelet countorbleedingtendencyshouldnotundergotheprocedure.
Thefollowingequipmentareneeded:• Gloves• Nasogastrictube(usually10Frenchorlarger)• 5, 10, 20 or 30 cc syringe, with appropriate connector for the
nasogastrictube• Litmus paper
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• Specimencontainer• Pen(tolabelspecimens)• Laboratoryrequisitionforms• Sterile water or normal saline (0.9% NaCl) Sodium bicarbonate
solution• (8%)Alcohol/chlorhexidine.
Procedure
Theprocedurecanbecarriedoutas:• An inpatient:first thing in themorningwhenthechildwakesup,
atthechild’sbedsideorinaprocedure-roomontheward(ifoneisavailable),oras
• Anoutpatient. The child shouldhave fasted for at least 4hours(infantsfor3hours)beforetheprocedure.
1. Findanassistanttohelp.2. Prepareallequipmentbeforestartingtheprocedure.3. Placeaplainsheet(orapapooseboardifavailable)onacouch.4. Positionthechildonhisorherbackwiththearmsstraightagainst
the side.5. Wrapthechildwiththesheettuckingthesheetunderthechild.The
assistantshouldhelptoholdthechild.6. Measurethedistancebetweenthenoseandstomach,toestimate
distancethatwillberequiredtoinsertthetubeintothestomach.7. Attachasyringetothenasogastrictube.8. Gentlyinsertthenasogastrictubethroughthenoseandadvanceit
intothestomach.9. Withdraw (aspirate) gastric contents (2–5ml) using the syringe
attachedtothenasogastrictubeandpourintoafalcontube.Add10. To check that the position of the tube is correct, test the gastric
contentswithlitmuspaper:bluelitmusturnsred(inresponsetotheacidicstomachcontents).Thiscanalsobecheckedbypushingsomeair(e.g.3–5ml)fromthesyringeintothestomachandlisteningwithastethoscopeoverthestomach.
11. Ifnofluidisaspirated,insert5–10mlsterilewaterornormalsalineandattempttoaspirateagain.
12. Ifstillunsuccessful,attemptthisagain(evenifthenasogastrictubeisinanincorrectpositionandwaterornormalsalineisinsertedintotheairways,theriskofadverseeventsisstillsmall).
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13. Donotrepeatmorethanthreetimes.14. Withdrawthegastriccontents(ideallyatleast5–10ml).15. Transfergastricfluidfromthesyringeintoasterilesputumcontainer.16. Addanequalvolumeofsodiumbicarbonatesolutiontothespecimen
(toneutralizetheacidicgastriccontentsandsopreventdestructionoftuberclebacilli).
After the procedure
Wipe thespecimencontainerwithalcohol/chlorhexidine topreventcross-infectionandlabelthecontainer.
Filloutthelaboratoryrequisitionforms.
Transport thespecimen (inacoolbox) to the laboratory forprocessingassoonaspossible(within4hours).
Ifitislikelytotakemorethan4hoursforthespecimenstobetransported,placethemintherefrigerator(4–8°C)untiltransported.
Givethechildhisorherusualfood.
Safety
Gastricaspirationisgenerallynotanaerosol-generatingprocedure.Asyoungchildrenarealsoatlowriskoftransmittinginfection,gastricaspirationcanbe considered a low risk procedure for TB transmission and can safely beperformedatthechild’sbedsideorinaroutineprocedureroom.
c) Procedure for Sputum InductionNotethat,unlikegastricaspiration,sputuminductionisanaerosol-generatingprocedure.Wherepossible,therefore,thisprocedureshouldbeperformedin an isolation room that has adequate infection control precautions(negativepressure,ultravioletlight(turnedonwhenroomisnotinuse)andanextractorfan).
Sputum induction is regarded as a low-risk procedure. Very few adverseeventshavebeenreported,andtheyincludecoughingspells,mildwheezingandnosebleeds.Recentstudieshaveshownthatthisprocedurecansafelybe
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performedeveninyounginfants,thoughstaffwillneedtohavespecializedtrainingandequipmenttoperformthisprocedureinsuchpatients.
General approach
Examinechildrenbefore theprocedure toensure theyarewellenough toundergotheprocedure.
Children with the following characteristics should not undergo sputuminduction.
• Inadequatefasting:ifachildhasnotbeenfastingforatleast3hours,postponetheprocedureuntiltheappropriatetime
• Severe respiratory distress (including rapid breathing, wheezing,hypoxia)
• Childrenwhoareintubated• Bleeding:lowplateletcount,bleedingtendency,severenosebleeds
(Symptomaticorplateletcount<50/mlblood)• Reducedlevelofconsciousness• Historyofsignificantasthma
Procedure1. Administerabronchodilator(e.g.salbutamol)toreducetheriskof
wheezing2. Administernebulizedhypertonicsaline(3%NaCl) for15minutesor
until5cm3ofsolutionhavebeenfullyadministered3. Give chest physiotherapy is necessary; this is useful to mobilize
secretions4. For older children now able to expectorate, follow procedures as
describedinsectionAabovetocollectexpectoratedsputum5. Forchildrenunable toexpectorate (e.g.youngchildren), carryout
either:I. Suction of the nasal passages to remove nasal
secretions;orII. Nasopharyngealaspirationtocollectasuitablespecimen
Anyequipmentthatwillbereusedwillneedtobedisinfectedandsterilizedbeforeuseforasubsequentpatient.
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Sputum smear examination
The test of choice for all child specimens is Xpert MTB/Rif.Inafewinstances,accesstoXpertMTB/RifforTBdiagnosismaynotbepossible.E.g.infacilitiesthatdonothaveanXpertMTB/Rifmachineandarenotlinkedtoonewherechildsamplescanbereferred.Insuchinstances,TBdiagnosisusingsputumforZNandFMmicroscopymaybedoneifavailable.
Itinvolvescollectionof2sputumsamples,aspotandamorningsampleasshownintable5.
Table 5: Spot and morning sputum collection strategy
Sample When is it collected? Where is it collected?
Spot 1st sample
Onthespotwhenchildpresentstofacility Inthehealthfacility
Morning2nd sample
Patientcollectsuponwakingupthefollowingmorning
Athomeandbringstohealthfacility(Orinhospitalifpatientishospitalized)
Instructthepatientandexplaintothemtheprocedureforexpectorationasabove.
Results should ideally be available within 24 hours after the sample issubmitted.
ZN and FM microscopy is also used for following up patients who werebacteriologically confirmedat diagnosis even if theywerediagnosedusingXpertMTB/Rif.
Culture and Drug Susceptibility Testing (DST)
CultureandsensitivityareusedtoconfirmadiagnosisofTBandtoevaluateifpatienthasanydrugresistance.Cultureisindicatedin:
• AllhighpatientsriskpatientswhoturnpositiveonXpertMTB/Rif• AllwithRifampicinresistanceonXpertMTB/Rifshouldhaveaculture
andDSTdone.
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ChildrenarecategorisedaslowandhighriskforDRTBasfollows:
Low risk for DR TB High risk for DR TB
• PeopleLivingwithHIVwithTBsymptoms
• Children<15yearswithTBsymptoms
• AllpresumptiveTBcaseswithanegativesmearmicroscopyresult
• PreviouslytreatedTBpatients:treatmentfailures,relapses,treatmentafterlosstofollowup
• ContactsofpatientswithDrugResistantTB• TBpatientswithapositivesmearresultat
month2ormonth5ofTBtreatment• ChildwhodevelopsTBsymptomswhileonIPT
orhashadpreviousIPTexposure• PrisonerswithTBsymptoms• RefugeeswithTBsymptoms
Chest Radiograph (Chest X-ray)Thechestradiograph(chestx-ray)isanimportantinvestigationfordiagnosisofTBinchildren.AclinicaldiagnosisofPTBmaybemadebycombiningsuggestivehistory,physicalexaminationfindingsandanabnormalCXR.PrimaryTBtendstobepredominantlyenclosedinhilarlymphnodesandthereforethebacilliareabsent insputum. Inthiscase, theCXRprovides importantsupport formakingaclinicaldiagnosisofPTBinchildren.
For children with history and physical signs suggestive of TB it is important to do a chest x-ray.
An abnormal CXR provides additional evidence to support the clinical diagnosis of PTB in children.
TheradiologicalfeaturesthatmaybesuggestiveofPTBinclude:• Enlargedhilarorsubcarinallymphnodes(checkfortheseonAPand
lateralviewsofthechestx-ray)• Lung opacification – especially if focal (segmental or lobar
opacificationcommon,butininfantsmaybepatchyopacificationinmanylobesasseeninbroncho-pneumonia)
• Diffuse micro nodular infiltrates throughout both lungs (milliarypattern)
• Olderchildrenandadolescents–upperlobeopacificationwi th orw i thout cavities.
OtherradiologicalfeaturesmaybesuggestiveofEPTB:a) Inthethoraciccavity,e.g.Pleuraleffusion(usuallyone-sided)b) Othersitesinthebodye.g.Boneandjointdisease,spinalTB
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Theimagesinfigure5showsomeoftheradiologicalchangesthatmayoccurwithPTB.
Figure 5: Pictures suggestive of Pulmonary TB
Right perihilar lymph node enlargement with opacity in the right mid-zone
Leftupperlobeopacificationwithnarrowingandshiftofleftmainbronchus
MilliaryTB:Typicalbilateraldiffusemicronodularpattern.NotedifferencestoLIPX-ray
above
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RadiologicalfeaturesthatmaysuggestextrapulmonaryTBvaryaccordingtotheaffectedsite.Examplesincludethoseinfigure6.
Figure 6: X-rays suggestive of extrapulmonary TB
LateralCXRshowingenlargedhilarlymph
nodes(“doughnutsign”)
PericardialTB:enlargedcardiacshadow.
Echocardiogramtodifferentiatefromothercausesofcardiacfailure
TBpleuraleffusion:largeleft-sidedeffusion.Pleuraltaptodifferentiatefrom
emphysema
SpinalTB:collapseofthoracicvertebracausingangulationina6-yearoldboy
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Tuberculin Skin Test (Mantoux test)
ApositiveMantouxtestisevidencethatoneisinfectedwithM.Tuberculosis,butdoesn’tnecessarilyindicatedisease.Correcttechniqueofadministering,readingandinterpretationofaMantouxtestisveryimportant.(SeeAnnex1)
Mantouxispositiveifindurationis:• ≥10mminawell-nourished,HIVnegativechild• ≥5mminamalnourished,orHIVinfectedchild
AnegativeMantouxdoesnotruleoutTB(especially intheHIVpositiveormalnourishedchild)
Interferon-Gamma Release Assays (IGRAs)
Haematological tests that can aid in diagnosing Mycobacterium tuberculosis infection e.g.QuantiFERONTBGoldIn-Tubetest(QFT-GIT)andT-SPOT®.TB test (T-Spot). It is an antibody-antigen test likeMantoux thatmeasuresthepresenceofanimmuneresponsetoTBbacilli.Thereislimiteddataonitsusein:
• Childrenyoungerthan5yearsofage• PersonsrecentlyexposedtoM. tuberculosis• Immunosuppressedpersonsand• Serialtesting
Other Tests for TB diagnosis• Radiologictestsinclude:
o CT scan – In complicated intracranial TB (tuberculoma,hydrocephalus,comatosechild)
o Ultrasound–usefulforabdominalTBandpleuraleffusion• Laboratorytests:Thesearemainlyusedinresearchsettings
o Nucleicacidamplificationtestso Gammainterferonassays
• Non specific tests like ESR and C- reactive protein tests suggestpresenceofinflammationifincreased.
• Biochemical tests – Elevated protein and low glucose levels incerebrospinalfluid(CSF),pleuralaspiratesorasciticaspiratessuggestanexudate.
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HIV test
Making a diagnosis of HIV infection has obvious implications for themanagementofTBandHIV.AllchildrenwithsuspectedTBshouldbetestedforHIV.(Refertochapter4).
Differential Diagnosis for Child with Chronic Cough/Respiratory SymptomsOtherconditionstoconsiderinachildwithchroniccough/chronicrespiratorysymptomswho does not fulfil the classical clinical picture of PTB includethoseintable6.
31
Table 6: Differential diagnosis for child with chronic cough/ Respiratory symptoms
Differential diagnosis Clinical Presentation
Asthma
Recurrentwheeze/cough–respondstobronchodilatorsUsuallyassociatedwithotherallergiessuchaseczema,rhinitis.
UpperairwayconditionsAllergicrhinitisAdenoidhypertrophy
Recurrent/persistentrunnynoseand/ornasalblockageandsnoringSeasonalpatternTriggers
ForeignBodyInhalation
UsuallysuddenonsetinpreviouslywellchildMayhavehistoryofchokingPersistentcoughOnesidedrespiratorysigns–inspiratorystridor,wheeze
Gastro-esophagealrefluxdiseaseRecurrentcough/wheezeOnsetinearlyinfancy+/-Hoarsevoice
Bronchiectasis
Severepersistentc o u g h ,muchsputum( ofteninfectedgreenoryellowincolour)FingerclubbingCXRshowsreticularorhoney-combpattern
CongenitalHeartDisease Easilyfatigability,breathlessness,Onsetearlyinfancy
AcquiredheartdiseaseOlderchildren,palpitat ions,easyfat igabi l i ty,dyspneaonexertion+/-oedema
Congenitalrespiratorydisorders
OnsetearlyinfancyCommonlyprematurebabyNoisybreathingduringinspirationnotrespondingtobronchodilators
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ThefollowingisasummaryofthealgorithmfordiagnosisofTBinchildren.
ALGORITHM FOR DIAGNOSIS OF PULMONARY TB IN CHILDREN
History of Presenting illness
Forallchildrenpresentingtoahealthfacilityaskforthefollowingsuggestivesymptoms:(Cough, fever, poor weight gain, lethargy or reduced playfulness)SuspectTBifchildhastwoormoreofthesesuggestivesymptomsAskforhistoryofcontactwithadult/adolescentwithchroniccoughorTBwithinthelast2years
Physical Examination
Examinethechildandcheckfor:•Temparature>37.5(fever)•Weight(toconfirmpoorweightgain,weightloss)-checkgrowthmonitoringcurve•Respiratoryrate(fastbreathing)•Respiratorysystemexamination-anyabnormalfindingsExamineothersystemsforabormalsignssuggestiveofextra-pulmonaryTB#
Investigations
Obtainspecimen*forXpertMTB/RIF(andculturewhenindicated**)DoachestXray(whereavailable)DoaMantouxtest***(whereavailable)DoaHIVtestDootherteststodiagnoseextra-pulmonaryTBwheresuspected#
Diagnosis
Bacteriologically confirmed TB:DiagnoseifspecimenispositiveforMTB
Clinically diagnosed TB:Child has two or more of the following suggestive symptoms:•Persistentcough,fever,poorweightgain,lethargyPLUStwo or moreofthefollowing:•Positivecontact,abnormalrespiratorysigns,abnormalCXR,positiveMantouxNote:IfthechildhasclinicalsignssuggestiveofEPTB,refertoEPTBdiagnostictable#
Treatment
Treat for TB as follows:•Allchildrenwithbacteriologically confirmed TB•Allchildrenwithaclinical diagnosis of TBNB:InchildrenwhodonothaveanXpertresult,ortheirXpertresultisnegative,but theyhaveclinicalsignsandsymptomssuggestiveofTBtheyshouldbetreatedforTBAllformsofTB(ExceptTBmeningitis,boneandjointTB):Treat for 6 months (2 RHZE / 4 RH)TBmeningitis,boneandjointTB:Treat for 12 months (2 RHZE/ 10 RH)
*Specimen may include: Expectorated sputum (child > 5 years), inducedsputum, nasopharyngeal aspirate and gastric aspirate.Attempt to obtain specimen in every child**DoacultureandDSTforthefollowingchildren:
1. RifampicinresistancedetectedbytheXperttest2. RefugeesandchildrenincontactwithanyonewhohasDrugResistant
TB3. ThosenotrespondingtoTBtreatment4. ThosewithIndeterminateXpertresults
***ThismayincludeIGRAinfacilitieswhereitisavailable# UseIMCIguidelinestoclassifyseverityofdiseaseRefertotable7ondiagnosisofExtra-pulmonaryTBintheguideline
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Table 7:Diagnosis of Extra-pulmonary TB in children
Site of EPTB Typical clinical presentation Investigations* Action
CervicalLymphadenitis(TBadenitis)
-Asymmetrical,matted,non-tenderlymphnodeenlargementformorethanonemonth+/-dischargingsinus-Commonlyinneckarea
-Fineneedleaspiration
±MantouxtestTreatforTBfor6months
Hilarlymphadenopathy
-Mayormaynothavecough-Noisybreathing-Fastbreathing,progressivebreathlessness-Asymmetricalwheezenotresponsivetobronchodilators
-ChestX-ray
±Mantouxtest
-TreatforTBfor6months-Includesteroidtherapy-Admitifhavingfeaturesofrespiratorydistress
TBmeningitis
-Headache-Irritability/abnormalbehaviour-Lethargic/reducedlevelofconsciousness,convulsions,neckstiffness,bulgingfontanel,cranialnervepalsies
-LumbarpuncturetoobtainCSF2-Infants-cranialultrasound-Olderchild;doCTscanbrain±Mantouxtest
-TreatforTBfor12months-HospitalizeforTBTreatment-Includesteroidtherapy
PleuralTB
-Shortnessofbreadth-Dullnessonpercussionandreducedbreathsounds+/-chestpain
-CXR-Pleuraltap1±Mantouxtest
-Ifpleuralfluidisstrawcoloured,treatforTBfor6months.-Addsteroidtherapy-IfpleuraltaprevealspusconsiderEmpyemaandrefer
AbdominalTB -Painlessabdominalswellingwithascites
-Ascitictap1
-Abdominalultra-sound4-±Mantouxtest
-TreatforTBfor6months
SpinalTB
-Painlessdeformityofspine-Mayhavelowerlimbweakness/paralysis-Gibbus
-APandLateralX-rayspine-±Mantouxtest
TreatforTBfor12monthsPhysiotherapyandoccupationaltherapyifindicated
PericardialTB-Cardiacfailure-Distantheartsounds-Apexbeatdifficulttopalpate
-CXR-Echocardiogram-±Mantouxtest
HospitalizeforTBtreatmentTreatforTBfor6monthsAddsteroidtherapy
TBboneandjoint(excludingspine)
-Painless,non-tenderswellingendoflongboneswithlimitationofmovement-Painless,non-tenderunilateraleffusionofusuallykneeorhip
-X-rayofaffectedboneand/orjoint-Jointtap-Mantouxtest
TreatforTBfor12months
1Typicalfindings:strawcolouredfluid,exudateswithhighprotein(formsawebonstanding),whitebloodcellsespeciallylymphocytes2Require 2 - 5ml of CSF. Do not attempt if there are signs of raised intracranial pressure (projectile vomiting, focalneurologicaldeficit,deterioratingmentalstatus)3Referralmaybenecessaryforinvestigationprocedureandlaboratorysupportaswellasclinicalcare.Ifreferralisdifficultornotreadilyavailable,startanti-TBtreatment.TheabovetablehighlightsthemorecommonformsofEPTB;however,TBmayinfectotherorgans.4Abdominalultra-soundillustratesabdominallymphadenopathyandshowscomplexascites+/-septation*Forallpaediatricspecimensexceptblood,XpertMTB/Rifisthetestofchoice.
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3.4 Intracranial Tuberculosis
In young children with signs and symptoms of meningitis, consider a diagnosis of TB Meningitis if there is history of
contact with a TB patient
IntracranialTBincludesTBmeningitis(TBM),tuberculomasandTBabscesses.TBMismorecommoninchildrenthaninadults,especiallyinthefirst5yearsof life. It isassociatedwithhighmorbidityandmortalityparticularly if thediagnosis is delayed.MilliaryordisseminatedTBhas ahigh risk (60–70%)ofmeningeal involvement.Forthisreason,allchildrenwithMilliaryTB(orsuspected of havingMilliary TB) should have a lumbar puncture done toexcludeTBmeningitis.
30%ofchildrenwithTBMarelikelytodiewhileover50%ofsurvivorsdevelopneurologicalsequelae.Earlydiagnosisandprompttreatmentarethuscrucialtoreducetheriskofapooroutcome.
ClinicalpresentationofTBMisusually insidiousandonemusthaveahighindex of suspicion. Presenting symptoms include irritability, headache,anorexia,photophobia, vomiting,andneck stiffness.Theymaypresentonabackgroundoflongstandingfeverandpoorweightgain.Inyoungchildren,symptomsmayprogress rapidly resulting indecliningmental status, comaanddeath.Occasionally,thesechildrenmaypresentwithfocalneurologicalsignse.g.nervepalsiesand/orhemiplegia.
Xpert MTB/RIF is the preferred diagnostic test for cerebrospinal fluid specimens from children suspected of having TB meningitis.Cautionmustbeemployedwhenconductingalumbarpuncture.Itmustnotbeattemptedwhen a child presents with signs of raised intracranial pressure (bulginganteriorfontanel,deterioratingmentalstatus,projectilevomiting,andfocalneurological deficit) due to the risk of brainstemherniation anddeath. Inchildren suspected to have raised intracranial pressure, a fundoscopy orimaging with CT scans may be necessary prior to attempting a lumbarpuncture.
Early initiation of treatment in children with intracranial tuberculosis isessential.ChildrenwithTBmeningitisshouldbehospitalizeduntilthechild
35
isclinicallystable.CorticosteroidshavebeenshowntoimprovesurvivalandreducemorbidityinTBmeningitisandarethusrecommendedinallcasesofTBM.
ComplicationsofintracranialTBinclude:• Obstructivehydrocephalus• Visualimpairment• Longstandingneurologicalimpairment
In patients with evidence of obstructive hydrocephalus and neurologicaldeterioration who are undergoing treatment for TBM, placement of aventricularshuntshouldnotbedelayed.Promptshuntingimprovesoutcome,particularlyinpatientspresentingwithminimalneurologicaldeficit.
36
CHAPTER 4
Treatment of Tuberculosis
Treatmentoutcomes inallchildrenaregenerallygoodprovidedtreatmentisstartedassoonasadiagnosis ismade.However,responsetotreatmentinHIVpositivechildrenmaybeslow.Childrengenerallytoleratetheanti-TBmedicinebetter thanadultsand theirdosagesarecalculatedaccording toweight(notage).Weightisimportantformonitoringtreatmentresponse.
Thegoalsofanti-TBtreatmentinchildrenareto:• CurethechildofTB• PreventdeathfromTB• PreventcomplicationsarisingfromTBdisease• PreventTBrelapse/recurrencebyeliminatingthedormantbacilli• Preventthedevelopmentofdrugresistancebyusingacombination
ofdrugs• ReduceTBtransmissiontoothers
4.1 Standard Operating Procedures for initiating anti-TB Treatment
• ClassifythecaseofchildTBbeforestartingtreatmentintopulmonaryor extra-pulmonary. For extra-pulmonary forms, specify the site,notingthatTBmeningitisandTBbone/jointistreatedfor12months,butallotherformsofTBaretreatedfor6months
• RecordtheTBdiagnosticcategory,treatmentregimenanddateanti-TBtreatmentwasstartedonroad-to-healthbookaswellasonTBtreatmentcardandfacilityTBregister
• A caregiver should be identified as the DOT (Direct ObservationTherapy)supporterforallagesincludingolderchildren.EducatetheDOTsupporteronanti-TBregimenandadherence
• Takethechild’sweightateachvisitandrecord• Once treatment is started it must be completed; “trial of TB
treatment” should never be used as a diagnostic tool
TreatmentregimenforTBinchildrenisshownintable9.
37
4.2 Recommended Treatment Regimen
ThedrugsusedforfirstlinetreatmentofTBinchildrenare:• Rifampicin(R)• Isoniazid(H)or(INH)• Pyrazinamide(Z)• Ethambutol(E)
Table8showstherecommendeddosages.
Table 8: Dosage of individual anti-TB drugs according to body weight
Drug RecommendationsAverage dose in mg/kg Range in mg/kg Maximum Dose
Isoniazid 10 7–15 300mg
Rifampicin 15 10–20 600mg
Pyrazinamide 35 30–40 2.0g
Ethambutol 20 15–25 1.0g
Thefirst3drugshavebeencombinedintopaediatricchild-friendlyfixeddosecombinations(FDCs)whicharedispersibleinliquid,haveapleasanttasteandarethereforeeasier forchildrento take.The improvedpaediatricTBFDCsprovide the correct dosing ratio of Rifampicin: Isoniazid: Pyrazinamide asfollows:
Rifampicin 75mg: isoniazid 50mg: pyrazinamide 150mg (RHZ 75:50:150) tablet
Rifampicin75mg:isoniazid50mg(RH 75:50)tablet
Ethambutolisavailableasasingledrugpaediatrictabletof100mg(E 100)Youngageinfluencesdrugmetabolism:aparticulardoseofadruginmg/kgwhengiventoayoungchild(under5years)maynotreachthesamelevelinthebloodaswhengiventoanolderchildoradult.Highermg/kgdosagesarethereforerequiredinyoungchildrentoachievebactericidallevels.
Pharmacokinetic studies show that the revised dosages will result in
38
higherbloodlevelsinyoungchildren,includingthoseunder2yearsofage.Systematicreviewoftheevidencealsoshowsthatthereviseddosageshaveanexcellentsafetyprofileandarenotassociatedwithan increasedriskoftoxicity (includingno increased riskofdrug inducedhepatotoxicitydue toisoniazidorpyrazinamide,orofopticneuritisduetoethambutol).
How to administer TB Treatment in children Treatmentisgivenintwophasesasfollows:
• The Intensive phase–thistakestwo months.Duringthisperiod,4medicinesareadministereddailytorapidlykillthebacilliinthebody(bactericidal).
• The Continuation phase–Thisvariesdependingon the typeofTBbeingtreated.Inthisphase,2drugsaregivendailytokilldormantandslowlymultiplyingbacillithatmaylingeraftertheintensivephase.AllformsofTBaretreatedforfour months inthecontinuationphaseexceptTBmeningitis,TBofthespine,boneandjointthataretreatedforten months.
Thisinformationissummarizedintable9.
Table 9: WHO recommended TB treatment regimen
TB disease categoryRecommended regimen
Intensive phase Continuation phase
AllformsofTB(ExceptTBmeningitisandTBofthebonesandjoints) 2monthsRHZE 4monthsRH
TBmeningitisTBofthebonesandjoints 2monthsRHZE 10monthsRH
DrugresistantTB RefertoaDRTBspecialistandinformCTLC
H=Isoniazid,R=Rifampicin,Z=Pyrazinamide,E=EthambutolFor previously treated children who present with symptoms of TB withintwoyearsof completinganti-TB treatment,evaluate fordrug resistantTB,progressiveHIVdiseaseorotherchroniclungdisease.MakeeveryefforttodiagnosethechildandmanageasperthealgorithmforTBdiagnosis.
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DOSAGES FOR PAEDIATRIC TB TREATMENT (IMPROVED FORMULATIONS)• During the intensive phase give paediatric FDC of RHZ dispersible
tabletsplusEtablets.• DuringthecontinuationphasegivepaediatricFDCofRHdispersible
tablets.Theregimeniscombinedasshownintables10to12below.
Table 10: Dosages for a child weighing up to 3.9 kg
Weight band (Kg)
Number of tablets
Intensive Phase Continuation Phase
RHZ (75/50/150mg)
E(100mg)
How to reconstitute the med-icines
RH(75/
50mg)
How to reconstitute the medicines
Less than 2Kg ¼ ¼
Dissolveone (1)tabletofRHZin 20 mlofsafedrinkingwater.
Oncefullydissolved,addthecompletelycrushedone (1)tabletofEthambutolandgive5ml (1/4) ofthissolutionmeasuredwithasyringe.
¼
Dissolveone (1)tabletofRHin20 mlofsafedrinkingwater.
Oncefullydissolved,give5ml (1/4)ofthissolutionmeasuredwithasyringe.
2–2.9 ½ ½
Dissolveone (1)tabletofRHZin 20mlofsafedrinkingwater.
Oncefullydissolved,addthecom-pletelycrushedone (1)tabletofEthambutolandgive10ml (1/2) ofthissolutionmeasuredwithasyringe.
½
Dissolveone (1)tabletofRHin20 mlofsafedrinkingwater.
Oncefullydissolved,give10ml (1/2)ofthissolutionmeasuredwithasyringe.
3–3.9 ¾ ¾
Dissolveone (1)tabletofRHZin 20 mlofsafedrinkingwater.
Oncefullydissolved,addthecom-pletelycrushedone (1) tabletofEthambutolandgive15ml (3/4) ofthissolutionmeasuredwithasyringe.
¾
Dissolveone (1)tabletofRHin20 mlofsafedrinkingwater.
Oncefullydissolved,give15ml (3/4)ofthissolutionmeasuredwithasyringe.
Ethambutol is not dispersible. Crush it completely before adding to thepreparedsolutionofRHZduringtheintensivephase.After giving the child their dose for that day, discard the rest of the solution. Prepare a fresh solution every day.
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Table 11: Dosages for a child weighing 4-25 kg
Weight band (Kg)
Number of tablets
Intensive Phase Continuation Phase
RHZ (75/50/150mg)
E(100mg)
How to reconstitute the medicines
RH(75/
50mg)
How to reconstitute the
medicines
4-7.9 1 1
Dissolvethetablet(s)ofRHZin 20 mlofsafedrinking
water.
Oncefullydissolved,addthecompletely
crushedtablet(s)ofEtham-butolandgiveALL this solutiontothechild.
1
Dissolvethetablet(s)ofRHin20 mlofsafedrinking
water.
OncefullydissolvedgiveALLthissolu-tiontothechild.
8-11.9 2 2 2
12-15.9 3 3 3
16-24.9 4 4 4
25kgandabove Useadultdosagesandpreparations
Table 12: Dosages for a child weighing 25kgs and above (adult formulation dosage table)
Weight band (Kg)
Number of tablets
Intensive Phase Continuation Phase
RHZE (150/75/400/275mg) RH(150/75mg)
25–39.9 2 2
40–54.9 3 3
55kgandabove 4 4
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Pyridoxine supplementation for children on TB treatmentIsoniazid is associated with a potential adverse effect of peripheralneuropathy.Childrenwhoaremalnourishedorwhohaveborderlinetolowlevelsofpyridoxine(vitaminB6)aremostatriskofdevelopingthisadversereactiontoINH.
ALLchildrenwhoareonanIsoniazid-containingtreatmentshouldbegivenpyridoxinethroughout the period of treatment, toprevent/minimizetheriskofIsoniazidtoxicity.
Therecommendeddosesofpyridoxinearegivenintable13.
Table 13: Pyridoxine (vitamin B6) dosing for children on TB treatment
Weight band (Kgs) Dose in mg Number of 25mg tablets Number of 50mg tablets
Less than 5 6.25mg Halfatablet3TIMESPERWEEK Notsuitableforyounginfant
5.0 – 7.9 12.5mg Halfatabletdaily Halfof50mgtablet3TIMESPERWEEK
8.0 – 14.9 25mg Onetabletdaily Halfof50mgtabletdaily
15 kg and above 50mg Twotabletsdaily One50mgtabletdaily
Other important observations to note include:• Report all children receiving anti-TB treatment to theNational TB
Program• Sideeffectsmayoccurbutarenotcommon.Themostimportantside
effectishepatotoxicity
Use of Ethambutol in childrenTheriskoftoxicity isnegligiblewhenEthambutol isusedatrecommendeddosagesof20(15-25) mg/kg/day.
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Riskoftoxicityisdose-relatedandrelatedtodurationoftherapy.Themainpotentialsideeffectisopticneuritisthatcanleadtoblindness.However,thedataonriskoftoxicityinchildrenhasbeenextensivelyreviewedandthereisnowalotofclinicalexperienceofitsuseinyoungchildren.
4.3 Additional Management Decisionsa) Hospitalization:
ThefollowingcategoriesofchildrenwithTBshouldbetreatedasin-patients:• SevereformsofPTBandEPTB(e.g.SpinalTB)forfurtherinvestigation
andinitialmanagement• TBmeningitisandotherformsofintracranialTB• Severemalnutritionfornutritionalrehabilitation• Signsofseverepneumonia(i.e.chestin-drawing)• Otherco-morbiditiese.g.severeanaemia• Socialorlogisticreasonstoensureadherence• Severeadversereactionssuchashepatotoxicity
b) Steroid therapy:Thisshouldbegiveninthefollowingsituations:
• TBmeningitisandotherformsofintracranialTB• PTBwithrespiratorydistress• PTBwithairwayobstructionbyhilarlymphnodes• SevereMilliaryTB• Pericardialeffusion
Giveprednisoneat2mg/kg oncedailyfor4weeks,thentaperdownover2weeks(1mg/kg for 7 days, then 0.5mg/kg for 7days).
c) For all HIV-infected childrenCommence Cotrimoxazoleprophylaxis (25 –30mg/kg once daily asshownintable26).Commence antiretroviral therapy within 2– 8 weeks of starting anti-TBtherapyaspertheARTguidelines.Conductfamily-basedcare/screeningforHIV.Referral of children with TB should be considered if:
• ChildhasseverediseaseasperIMCIguidelines• Diagnosisisuncertain• NecessityforHIV-relatedcaree.g.tocommenceART• Failuretorespondtotreatmentdespitegoodadherence
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4.4 Follow-up of a Child on anti-TB TherapyChildren on treatment for TB are routinely followed up to assess forimprovementandadherence to treatment. Someof the investigationsarerelevantaspartof treatment followup.Thekey featuresof followuparespecifiedintable14.Table 14: Follow up of a child on TB treatment
Month Baseline 1 2 3 4 5 6 7 8 9 10 11 12
ClinicalreviewforbothPTBandEPTB(symptomassessment,drugtoxicityandadherence)
Everyweek Everytwoweeks
Weight(doseadjustment) Everyweek Everytwoweeks
Height/WeightforHeightZ-score/BMIforage
XpertMTBRIF(Donefordiagnosis.Mayrepeatatanyotherpointifdrugresistanceissuspected)
Smearforfollowupinbac-teriologicallyconfirmedTB
CultureandDST(ifnotimproving/suspectedresistance)
Seealgorithm
Viralload(forHIVinfected)
CXR Repeatifnotrespondingtotreatmentatanypoint
MonitoringofachildwithEPTBshouldbeconductedbasedonthesiteofdisease.
4.5 Poor Response to TreatmentMostchildrenwithTBwillstarttoshowsignsofimprovementwithinamonthofanti-TBtreatment.Weightgainisasensitiveindicatorofgoodresponsetotreatment.ChildrennotrespondingtoTBtreatmentafteronemonthshouldbereassessedforcausesofthepoorresponseandpossibledrugresistance.
TB treatment should however not be stopped.Potentialcausesofpoorresponsetotreatmentinclude:
• Pooradherence;HIVinfection• Wrongdiagnosis• Otherconcurrentchroniclungdiseases
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• Underdosageofdrugs• ResistantformofTB• Complicationse.g.neurologicalcomplications,bronchiectasis
Considertreatmentfailureifchildisreceivinganti-TBtreatmentand:• Thereisnosymptomresolutionorsymptomsaregettingworse. In
thiscase,alwaysconfirmifadherence isgood. Ifuncertain,achildcanhavehealthcareworkerDOTatthehealthfacility
• Thereiscontinuedweightloss• If child was bacteriologically confirmed at diagnosis and remains
smearpositiveatmonth2or5
Referchildrenwithsuspectedtreatmentfailureforfurtherassessment.
Poor adherence is the most common cause of poor response to treatment. If uncertain a child can have a health care worker
DOT at the health facility
Importance of Adherence to Treatment• Reducesdiseasetransmission• Reducerelapses• Increasecurerate• Reducedefaulterrate• Reducesmortality• Reduces the emergence of drug resistance (multi drug resistant
strains)Ways to improve adherence
• Explainandemphasize tocare-giverandchildwhy theymust takethefullcourseoftreatmenteveniftheyarefeelingbetter
• Note risk factors for poor adherence such as distance/transport;orphan(especiallyifmotherhasdied)orprimarycare-giverunwell;adolescents
• EducationandadherencesupportespeciallyTB/HIV• Explainthatanti-TBdrugsinchildrenarewelltoleratedandsafe
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4.6 Treatment InterruptionsIfachild interruptsanti-TBtreatment foraperiod less than2consecutivemonths, continuewith their TB treatmentwhen they resume and extendtreatmenttocovertheperiodmissed.
If the child interrupts anti-TB therapy for a period longer than 2months,conduct an Xpert test when they resume and start them on a treatmentregimenbasedonXpertMTB/Rifresults.
4.7 Adverse drug reactions of anti TB drugs in childrenAdverseeventscausedbyanti-TBdrugsaremuchlesscommoninchildrenthaninadults.
Themostimportantsideeffectishepatitis,whichmaypresentwithnauseaandvomiting.Presenceofabdominalpain,jaundiceandatenderenlargedliversuggestseverehepatotoxicity.
INHmay cause symptomaticpyridoxinedeficiency; particularly in severelymalnourishedchildrenandHIVinfectedchildrenonhighlyactiveantiretroviraltherapy(HAART). Itmanifestsastingling,numbnessandweakness.Achildmay also present with reduced playfulness. Supplemental pyridoxine isrecommendedforall childrenonTBtreatmentoronIsoniazid.
OthersideeffectsthatmaybeexperiencedwhilethechildisonTBtreatmentareasshownintable15.
Table 15: Other important adverse effects
Drug Adverse effects
Isoniazid PeripheralneuropathyHepatitis
RifampicinHepatitisRedcolouredbodyfluidsDruginteractionswithARVs,warfarin,insulin,oralcontraceptives
Pyrazinamide HepatitisArthralgia
Ethambutol Opticneuritis
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4.8 Managing Drug Toxicities
Peripheral neuropathy• Maybepotentiatedbyotherneurotoxicdrugs(DDI,d4t),alcoholism,
metabolicdisease(diabetes),malnutritionandinfections• Rarelysevereenoughtorequiredrugwithdrawal• Preventablewithlowdosesupplementalpyridoxine(Table13)• Treatedwithhighdosepyridoxine(25-50mg/day)• Relief of symptoms can be done using Analgesics, Tricyclic
antidepressants (amitriptyline, nortriptyline), Anticonvulsants(carbamazepine,phenytoin)
Anti-TB drug induced hepatitis• Elevationofliverenzymesmayoccurinthefirstweeksoftreatment.
Serumliverenzymelevelsdonotneedtobemonitoredroutinely,asasymptomaticmildelevationofserumliverenzymes(lessthanfivetimesthenormalvalues)isnotanindicationtostoptreatment
• All childrenwith gastrointestinal symptoms (nausea and vomiting,livertenderness,hepatomegalyorjaundice)shouldhavetheirliverfunctionassessed
• Elevation of liver enzymes less than 5 times the normal without symptoms: continue TB treatment but closely monitor the liverfunctionsandconsiderseniorreview
• Elevation of liver enzymes less than 5 times the normal with symptoms: stopallanti-TBsandreferforfurthermanagement
• If the liver enzyme levels are elevated to more than 5 times the normal, stopallant-TBsandreferforfurthermanagement.Considerin-patientmanagement
• Patientsshouldbescreenedforothercausesofhepatitis(thehepatitisviruses-A,B,C),andnoattemptshouldbemadetoreintroducethesedrugsuntilliverfunctionshavenormalized.Anexpertwithexperienceinmanagingdrug-inducedhepatotoxicityshouldbeinvolvedinthefurthermanagementofsuchcases
Ethambutol toxicity• ThisisrareifchildistreatedwithEthambutoldosesthatarewithin
therecommendeddoserangeof15to25mg• Early signs of Ethambutol toxicity can be tested in the older child
throughvisualassessment
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• PatientswhodevelopEthambutoltoxicityshouldnotbetreatedwithEthambutolagainandshouldbeadvisednevertotakethedrugagainintheirlifetime
4.9 Treatment outcomes for children on treatment for TB
Treatment outcome definitions (excluding children treated for RR-TB and MDR-TB)Thenew treatmentoutcomedefinitionsmakea cleardistinctionbetweentwotypesofpatients:
i) Patientstreatedfordrug-sensitiveTBii) Patientstreatedfordrug-resistantTBusingsecond-linetreatment
(defined as combination chemotherapy for drug-resistanttuberculosiswhichincludesdrugsotherthanthoseinGroup1)
The two groups are mutually exclusive. Any patient found to have drug-resistant TB and placed on second line treatment is removed from thedrug-sensitiveTBoutcomecohortand includedonly in thesecond-lineTBtreatmentcohortanalysis.ThismeansthatmanagementofthestandardTBregisterandofthesecond-lineTBtreatmentregisterneedstobecoordinatedtoensureproperaccountingoftheoutcomesoftreatment.
Treatment outcomes for drug sensitive TB patients All bacteriologically confirmed and clinically diagnosed TB cases who aresensitiveto1stlinedrugsshouldbeassignedanoutcomefromthelistintable16.
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Table 16: Treatment Outcomes for Drug Sensitive TB Patients
Outcome Definition
Cured
ApulmonaryTBpatientwithbacteriologicallyconfirmedTBatthebeginningoftreatmentwhowassmearorculturenegativeinthelastmonthoftreatmentandonatleastonepreviousoccasion.
Treatment completed
ATBpatientwhocompletedtreatmentwithoutevidenceoffailureBUTwithnorecordtoshowthatsputumsmearorcultureresultsinthelastmonthoftreatmentandonatleastonepreviousoccasionwerenegative,eitherbecausetestswerenotdoneorbecauseresultsareunavailable.
Treatment success Thesumofcuredandtreatmentcompleted.Thisiscalculatedbasedonbacteriologicallyconfirmedcases.
Treatment failed ATBpatientwhosesputumsmearorcultureispositiveatmonth5orlaterduringtreatment.
Died ATBpatientwhodiesforanyreasonbeforestartingorduringtreatment.
Lost to follow-upATBpatientwhodidnotstarttreatmentorwhosetreatmentwasinterruptedfor2consecutivemonthsormore.
Not evaluated
ATBpatientforwhomnotreatmentoutcomeisassigned.Thisincludescases“transferredout”toanothertreatmentunitaswellascasesforwhomthetreatmentoutcomeisunknowntothereportingunit.
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CHAPTER 5
Management of Tuberculosis in HIV infected children
MostpaediatricHIVinfectionoccursprenatallythroughverticaltransmission.HIV disease progresses rapidly in childrenwith ~50% of them developingsevere immune-suppression and dying before 2 years of age if they donot access anti-retroviral therapy. In this setting,when these children areinfectedwith TB, TB progresses evenmore rapidly to severe diseasewithhighmortality. These children are at high risk of TB infection as they liveinhouseholdswhereaparentisalsolikelytohaveHIVdiseaseandhaveahigher probability of developing active TB. Similarly, TB co-infection itselfcausesmorerapidprogressionofHIVdisease.
HIVinfluencesTBinseveralways:• RapidprogressionofnewTBinfectiontoTBdisease• IncreasedriskofdisseminatedandcomplicatedTBdisease• ReactivationoflatentTBinfection(olderchildrenandadolescents)• Poor response to TB treatment in the child with severe immune-
suppression• Increased risk of relapse or recurrence of TB after successful
treatment• IncreasedriskofdeathfromTBHIVco-infection• Increasedriskofmultipleco-infectionsinadditiontoTB,e.g.bacterial
pneumonia,pneumocysticcariniipneumonia
HIVinfectedchildrenmayhavemultipleandconcurrentopportunisticlunginfectionsthatclinicallypresentlikeTB,thusmakingthediagnosisofTBinaHIVinfectedchildmoredifficult.TheARVsandanti-TBdrugshavepotentiallysignificantdrug-druginteractionsaswellasoverlappingtoxicitiesthatposeadditional challenges in treating co-infections. Therefore, comprehensiveapproachtomanagementofbothTBandHIViscritical.
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5.1 Diagnosis of TB in HIV
Approach to diagnosis of TB in HIV infected children is similar as for HIVuninfected children. History of contact with TB is extremely important inpointingtopossibilityofTBdiseaseinayounger,HIVinfectedchild.
The clinical presentationof TB is similar between those in early stages ofHIV disease and those without HIV. However, those with advanced HIVdiseasemaynothavethetypicalTBclinicalfeatures,andchronicrespiratorysymptomsmaybedue toother causes. TheymayalsopresentwithextrapulmonaryTB.(See table 7).
Allhealthcaresettingsshould implementTB infectioncontrolguidelinestoreducetheriskoftransmissionofTBbetweenpatients,visitorsandstaff.Symptom-basedTBscreeningusingtheIntensifiedCaseFindingtoolMUSTbeperformedforallchildrenlivingwithHIVateveryclinicvisittoruleoutactiveTB;patientswhoscreenpositive(presumptiveTBcases)mustbeevaluatedaccording to thealgorithm for TBdiagnosis. Patientswho screennegativeshouldbe initiatedon IsoniazidPreventiveTherapy (IPT). The screening isdoneusingatoolasshownintable17and18.
Table 17: Paediatric Intensified Case Finding Screening Tool
Screening Questions Y/N
1.Coughofanyduration(Y/N)
2.Fever(Y/N)
3.Failuretothriveorpoorweightgain(Y/N)
4.Lethargy,lessplayfulthanusual(Y/N)
5.ContactwithaTBcase(Y/N)
• If “Yes” to any of the above questions, suspect TB, examine the child and use the paediatric TB diagnosticalgorithmtoevaluateforactivedisease.Ruleoutunderlyingconditions,referifnecessary
• If“No”toallquestions,initiateworkupforIPTandrepeatscreeningonsubsequentvisits
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Table 18: Adolescent and Adult Intensified Case Finding Screening Tool
Screening Questions Y/N
1.Coughofanyduration
2. Fever
3.Noticeableweightloss
4.Nightsweats
• If“Yes”toanyquestion;takeadetailedhistory,examinethepatientanddosputumexamination ifcoughing(sputumsmearorGeneXpert).Excludeunderlyingillnesses
• If“No”toallquestions,initiateworkupforIPTandrepeatscreeningonsubsequentvisits
Xpert MTB/Rif test is the recommended 1st test for diagnosis of TB and Rifampicin resistance in all-presumptive TB cases.
Together with TB symptoms, a positive Mantoux test is suggestive of TBdisease.ApositiveMantouxtestwithoutsymptomsor featuressuggestiveofTBshouldnotbeusedtodiagnoseTB inchildren (seealgorithmforTBdiagnosis in children). Any childwith a positive XpertMTB/RIF test resultshouldbestartedonantiTBtreatment.AnegativeXpertMTB/RIFtestresulthoweverdoesn’t indicatethechildhasnoTB; furtherclinicalevaluation isneededtomakeaclinicaldiagnosisofTBinsuchchildren.
5.2 Diagnosis of HIV in TB
HIVtestingshouldbevoluntaryandconductedethicallyinanenvironmentwherethefiveCsofConsent,Confidentiality,Counseling,CorrectresultsandConnection(linkage)canbeassured.
ForallchildrenandadolescentswithTB,conductHIVtestingandcounselling(withparental assent). Infants shouldbe testedaccording to theavailableguidelines for HIV diagnosis in infants aged <18 months. A positive HIVantibodytestinachildyoungerthan18monthsofageconfirmsHIVexposure.
AllHIVExposedInfants(HEI)shouldbetestedwithDNAPCRwithin6weeksofageor1stcontactthereafter,andifnegativethenanotherDNAPCRat6months,andifnegativethenanotherDNAPCRat12months.This replaces previous guidelines to perform antibody testing for infants at 9 months.
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AnantibodytestshouldbeperformedforallHEIat18months,and6weeksaftercompletecessationofbreastfeeding.Adolescentsaged15yearsandaboveandemancipatedminorscanprovideself-consent. For younger adolescents, obtain their assent and parental/caregiverconsent.LinkallchildrenandadolescentsidentifiedasHIVpositivetotreatmentandpreventionservices.
5.3 Differential Diagnosis in a HIV infected Child with Chronic Respiratory Symptoms
ThediagnosisofPTBcanbeparticularlychallenging inaHIV-infectedchildbecause of clinical and radiological overlap with other HIV-related lungdisease.Therespiratorysystem isacommonsite formanyopportunistic infectionsinHIV infected children.Often there is co-infection aswell,which furthercomplicatesthediagnosis,otherpossiblecausesofchronic lungdisease inHIVinfectedchildrenareshownintable19.
Table 19: Differential diagnosis of chronic respiratory symptoms in HIV infected childrenDifferential Diagnosis Clinical features
TuberculosisPersistentrespiratorysymptomsnotrespondingtoantibiotics.Oftenpoornutritionalstatus;positiveTBcontactespeciallyinyoungerchildrenCXR:focalabnormalitiesandperihilaradenopathy
Recurrentpneumonia Recurrentepisodesofcough,feverandfastbreathingthatusuallyrespondtoantibiotics
LymphoidInterstitialPneumonitis
Slowonsetcoughassociatedwithgeneralizedsymmetricallymphadenopathy,fingerclubbing,parotidenlargement,variablenutritionalstatus,mildhypoxia,CXR:diffusereticulonodularpatternandbilateralperihilaradenopathy
Bronchiectasis
Cough,productiveorpurulentsputum,halitosis,fingerclubbing,seeninolderchildren.CXR:honeycombingusuallyoflowerlobesComplicatesrecurrentbacterialpneumonia,LIPorTB
PneumocystisJeroveciiPneumonia
Commoncauseofacuteseverepneumonia,severehypoxiaespeciallyininfants.Unusualafter1yearCXR:diffuseinterstitialinfiltration,hyperinflation
Mixedinfection Commonproblem:LIP,bacterialpneumonia,ConsiderTBwhenthereispoorresponsetofirst-lineempiricmanagement
Kaposi’ssarcoma UncommonCharacteristiclesionsonskinorpalate
53
Bronchiectasis: focal opacification in right lower zone with thickening of bronchial walls and honeycomb appearance
Lymphoid interstitial pneumonitis: typical features are bilateral, diffuse reticulonodular infiltration with bilateral perihilar lymph node enlargement
5.4 Treatment of the TB/HIV co-infected child
Asstatedearlier,TBinfectionprogressesrapidlytoseverediseaseanddeathinchildren,andevenmorerapidlyiftheyhaveHIV.
Once a diagnosis of TB is made in a HIV infected child, TB treatment should be initiated as a matter of urgency,
regardless of whether the child is on ART or not
Withthe2016ARTguidelinesall PLHIV now qualify for ART irrespectiveofWHOClinicalStage,CD4count,age,gender,pregnancystatusorco-infectionstatus etc. Any child with active tuberculosis should begin TB treatmentimmediately;andbeginARTassoonastheTBtreatmentistolerated;i.e.nonauseaorvomitingandnoon-goingorevolvingadversedrugevents,usually2to8weeksintoTBtherapy.
Post-test counselling should, at a minimum, include three key messages that begin the ART treatment preparation process for all PLHIV:
• Treatment (called antiretroviral therapy orART) is available and isrecommendedforeveryonewithHIV
• Startingtreatmentassoonaspossible(preferablywithintwoweeksoftestingpositiveforHIV)reducesthechanceofyourillnessgetting
54
worseorofpassingHIVtoothers• IfyoutakeyourARTproperlyanddonotmisspillsyoucanexpectto
livealongandproductivelife
Laboratory assessment is not a prerequisite to ART initiation. It should not cause undue delay in starting ART following treatment preparation and clinical evaluation by
history and physical examination
AllpatientsenrollingintoHIVcareshouldhaveacompletemedicalhistorytaken, a thorough physical examination and appropriate laboratoryinvestigations. Important baseline investigations are shown in table 20.However,ARTshouldnotbedelayedifalaboratorytestisnotavailable.
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Table 20: Baseline Laboratory Investigations for PLHIV
HIVSpecific
Test Comments
ConfirmanddocumentpositiveHIVtestresult Aspertestingguidelines
CD4cellcount
•Recommended•IfCD4≤100cells/mm3thenlaboratoryshouldperformaserumcryptococcalantigen(sCrAg)onthesamesampletoruleoutcryptococcalmeningitisbeforestartingART
Viralload(HIV-1RNA)
•Baselineviralload(VL)isonlyrecommended(whereavailable)forHEIsafter1stPCRtestispositive.SpecimenforbaselineVLcanbedrawnbeforeorattimeofinitiatingART;obtainingaVLshouldnotdelayARTinitiation
SerumCryptococcalAntigen(sCrAg)
•ObtainserumCrAginalladultswithaCD4count≤100cells/mm3
•Ifpositive,manageasperthecryptococcalmeningitisscreeningalgorithm(RefertotheKenyaARVguidelines)
Hb(preferablyfullbloodcountifavailable)
•Recommended•IfbaselineHb<9.5g/dLthenAZTshouldbeavoided
Pregnancystatus•Pregnancystatusshouldbedeterminedforallwomenofreproductiveage(basedonhistoryoflastmenstrualperiod,andifdelayedthenaurinepregnancytestshouldbeperformed)
Urinalysis(forprotein&glucose)
•Recommended
Creatinine•Recommended•CalculateCreatinineClearance(CrCl):ifCrCL≤50ml/minthenTDFshouldbeavoided
RPR(syphilisserology) •Recommended(forallPLHIVwithahistoryofbeingsexuallyactive)
Glucose •Recommended
Plasmalipidprofile •Recommended
HBsAg
•Recommended•Ifnegative,patientsshouldbeimmunizedforHBVassoonastheyachieveconfirmedviralsuppression;ifpositiverefertoARVguidelineformanagementofHIV/HBVco-infection
HCVantibody •RecommendedforPWIDorforpatientswithhistoryofinjectiondruguse
ALT
•Notarecommendedbaselineinvestigationunlessthereisaspecificclinicalreason(e.g.patientwithhistoryofhepatitis,signsorsymptomsofliverdisease,orriskofliverdisease-alcoholics,HBV/HCVinfection,hepatotoxicdrugs,etc.)
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Managementofthesechildrenrequirestakingnoteofthefollowingpossiblescenariosforeachchildassummarizedinfigure7,toguidehowandwhentogiveboththeanti-TBandtheARTtreatment.
Scenario 1ChildrenwhoarenotyetonART
-Startanti-TBimmediately-InitiateARTassoonasanti-TBmedicationsaretolerated,preferablywithin2-4weeks
Scenario 2ChildrenwhoarealreadyonARTbuthavereceiveditforlessthan6months
-Startanti-TBimmediately-ContinueART,makinganyrequiredadjustmentstotheART regimenbasedonpredicteddruginteractions
Scenario 3ChildrenwhoarealreadyonARTbuthavereceiveditformorethan6months
- Startanti-TBimmediately- Evaluate for possible treatment failure making any requiredadjustmentstotheARTregimen.ContinueART,basedonpredicteddruginteractions
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Figure 7: Management of HIV in a child with TB
Sce
Newly di
Start ART aTB medic
toleratedw
nario 1
agnosed HI
as soon as acines are wed within 2-4
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N
S
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ad
New TB diagchil
Establish H
Start anti TB
Scenar
nown HIV pmonths o
Continue oART in addi
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Make anydjustments
regim
gnosis in ald
HIV status
B treatment
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positive < 6on ART
on currentition to antiication
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Scenario
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aluate the chreatment fa
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TheprinciplesoftreatmentoftuberculosisinHIV-infectedchildrenaresimilartothoseinHIV-negativechildren,andthesameregimensshouldbeusedasthoseusedinHIVnegativechildren.However,responsetoTBtreatmentmaybeslowinchildrenlivingwithHIV.
AllchildrenwithTB/HIVshouldreceiveCotrimoxazoleprophylaxisaswellasantiretroviraltherapy.NutritionalsupportisoftenneededforchildrenwithTB/HIV.
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Themanagementof childrenwithTB/HIV shouldbe integrated so thatallfamily members are counselled and tested for HIV, screened for TB andmanagedappropriately.
Healthcare settings present suitable conditions for transmission of TB;particularlyamongvulnerable individuals likePLHIV.AllhealthcaresettingsshoulddevelopandimplementTBinfectioncontrolguidelinestoreducetheriskoftransmissionofTBbetweenpatients,visitorsandstaff.
5.5 Antiretroviral Therapy in HIV Infected Child with TB
Tuberculosis is an increasingly common opportunistic infection in HIV-infectedchildren.HIVinfectionincreasesachild’sriskofprogressiveprimarytuberculosisandreactivationoflatentTBintheolderchild.
Recent data suggest that early initiation of HAART early in TB treatmentreducesTBmorbidityandmortality,withoutexcessadverseevents.
AnychildwithactivetuberculosisshouldbeginTBtreatment immediately;andbeginARTas soonas theTB treatment is tolerated; i.e.nonauseaorvomiting and no on-going or evolving adverse drug events, usually 2 to 4weeksintoTBtherapy.
TheTB/HIVco-infectedchildhasnotonlydiagnosticbutalsodrugmanagementchallenges.ThepillburdeninTB/HIVco-infectionislarge.Intensiveadherencesupportandmonitoringshouldbeoffered.Theriskofadversedrugreactionsis increased during concomitant therapy. Perform a full clinical evaluationat every clinic visit and if there are symptoms suggestive of adverse drugreactions,particularlylivertoxicity,referthechild.
Therearesignificantdrug-drug interactionsbetweentheARVsandanti-TBmedications,overlappingtoxicitiesbetweenthesetwoclassesofmedicationsand a highpill burden. Rifampicin interactswith both PIs andNevirapine,reducing their blood levels and hence their effectiveness. Therefore,whentreatingTBandgivingconcurrentART,theARTregimenmayrequireadjustment.
If significantproblemsareexperienced suchas severedrug intoleranceorerraticadherence,continuetheanti-TBandreferthechildtoaHIVclinical
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managementteam/specialist.
EffectiveART consists of aminimumof 3 agents from at least 2 differentclassesofARVs.ARToptionswithRifampicinare limitedandarebasedonthevariousscenariosasindicated.
• EFVbasedART• SuperboostedLPVwithritonavirduringTBtreatmentandrevertto
thenormalLPV/rdosingaftercompletionofTBtreatment• Triple nucleosides- Triple nucleoside ART has a likelihood of
developingvirologictreatmentfailure
Use of AZT+ABC+3TC may lead to accumulation of mutations. It shouldbe used only when other options are not indicated or available or whenpreferredoption isnottoleratedandchildneedstobeputonARTduetosevereimmunesuppression.
Always weigh the child and adjust the TB and ARV dosing accordingly
Refer to national guidelines on Anti-retroviral therapy for Paediatric ARV dosing
Triple nucleoside ART should NOT be used in TB/HIV co-infected patients who have previously failed ART
The preferred ART Regimens for childrenwith TB/HIV Co-infection are asshownintable21and22.
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Table 21: Preferred ART Regimens for TB/HIV Co-infection for Children Newly Initiating 1st Line ART
Age 1st Line if TB/HIV Co-infection
<4weeksStartanti-TBtreatmentimmediatelyStartARTafter4weeksofage,oncetoleratinganti-TBdrugs(followtheregimenrecommendationsforchildren4weeksto<3yearsofage)
4weeks-<3years
•ABC+3TC+LPV/r+RTV(1,2)•Ifnotabletotoleratesuper-boostedLPV/r+RTVthenuseAZT+ABC+3TCfordurationofTBtreatment•AftercompletionofTBtreatmentreverttotherecommended1stlineregimen(ABC+3TC+LPV/r)
3-15years(<35kgbodyweight) ABC+3TC+EFV
3-15years(≥35kgbodyweight) TDF+3TC+EFV
>15years TDF+3TC+EFV
PWID>15years TDF+3TC+ATV/r(usingRifabutin-basedanti-TBtreatment)
1 Use “super-boosted” LPV/r by adding additionalRitonavir suspension to manage the drug interactionbetween LPV/r and Rifampicin (see Table 25 for LPV/rdosing recommendations). As soon as TB treatment iscompleted the child should goback to standard LPV/rdosing. For children who cannot tolerate LPV/r + RTV(usually because of GI side-effects), the alternativeregimen is AZT+ABC+3TC; as soon as TB treatment is completed the child should go back to ABC+3TC+LPV/r, because of the increased risk of developing treatment failure while on a triple-NRTI regimen 2EFVisnolongerrecommendedforchildren<3yearsoldbecauseof highly variable EFVmetabolismat thatage
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Table 22: Preferred ART Regimens for TB/HIV Co-infection for Patients Currently on 1st Line ART 1, 2
Current Regimen3 Age Recommended Substitution
PI/r-based AZT+3TC+LPV/rABC+3TC+LPV/rTDF+3TC+LPV/rABC+3TC+ATV/rAZT+3TC+ATV/rTDF+3TC+ATV/r
<3yearsold
•Super-boostLPV/rwithadditionalRTV4
•Ifnotabletotoleratesuper-boostedLPV/r+RTVthenuseAZT+ABC+3TCforthedurationofTBtreatment5
•After completion of TB treatment revert to the original regimen
3years–15years(weight<35kg)
SwitchtoEFV.IfEFVcannotbeused,super-boostLPV/rwithadditionalRTVtoaratioof1:1
Child<15yearsand≥35kg ContinuePI/r;useRifabutin6foranti-TBtreatment
>15years(anyweight) ContinuePI/r;useRifabutinforanti-TBtreatment
EFV-basedABC+3TC+EFVTDF+3TC+EFVAZT+3TC+EFV
Anyage Continuesameregimen
NVP-based7
AZT+3TC+NVPABC+3TC+NVPTDF+3TC+NVP
<3yearsold SwitchtoAZT+ABC+3TC(as soon as TB treatment is completed switch back or original regimen)
≥3yearsold SwitchtoEFV
RAL-basedABC+3TC+RALAZT+3TC+RALRAL+3TC+DRV+RTVAZT+RAL+3TC+DRV+RTVAZT+RAL+3TC+DRV+RTV
Allages GivedoublethestandarddoseofRAL
1 AlwaysassessforHIVtreatmentfailureinpatientswhodevelopTBafterbeingonARTfor_6months2 Forpatientson2ndlineART,subsequentregimens,ornon-standarddrugssuchasRALorDTGwhorequireregimenchangebecauseofTBtreatment,consulttheRegionalorNationalHIVClinicalTWG([email protected])3NRTIsinthepatient’scurrentregimendonotrequireanyadjustmentswithanti-TBtreatment4Use“super-boosted”LPV/rbyaddingadditionalRitonavirsuspensiontomanagethedruginteractionbetweenLPV/randRifampicin(seeTable8.7fordosingrecommendations).As soon as TB treatment is completed the child should go back to standard LPV/r dosing5ForchildrenwhocannottolerateLPV/r+RTV(usuallybecauseofGIside-effects),thealternativeregimenisAZT+ABC+3TC;as soon as TB treatment is completed the child should go back to ABC+3TC+LPV/r, because of the increased risk of developing treatment failure while on a triple-NRTI regimen6Rifabutin150mgoncedailyinplaceofRifampicin.WhenusingRifabutin,closelymonitorforsideeffectse.g.neutropenia,neurotoxicityanduveitis7Guidelines recommend LPV/r for children < 3 years, however some children < 3 years maybe on NVP due to LPV/r toxicity
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Table23belowgivesthenamesandabbreviationsofARVs.Table 23: Abbreviations and Names of Antiretroviral Drugs
3TC Lamivudine DRV Darunavir LPV/rLopinavir/
Ritonavir
ABC Abacavir DRV/r Darunavir/Ritonavir NVP Nevirapine
ATV Atazanavir DTG Dolutegravir RAL Raltegravir
ATV/r Atazanavir/Ritonavir EFV Efavirenz RTV Ritonavir
AZT Zidovudine LPV Lopinavir TDF Tenofovir Disoproxil Fuma-rate
RifabutinThisisananti-TBdrugoftheRifamycinsgroup.Itisgivenatadoseof150mgoncedailythroughouttheTBtreatmentofthechild. It isgiventochildrenabove theweightof35kgwhoareonaPI-basedregimenwhomaysufferseveresideeffectsfromsuper-boostingthePI.ForchildrenwhoareonanEfavirenz-basedregimen,thedosingscheduletobeusedisasshownintable24.
Table 24: Efavirenz dosage in children
Weight (kg) EFV dose (mg) Tablets Quantities
3.5to4.9 100 ½ of 200mg single scored tablet
5to7.4 150 3of50mgcapsules
7.5to13.9 200 1tabletofthe200mgtablet
14to19.9 300 ½tabletofthe600doublescored
20to24.9 300 1½ofthe200mgsinglescored
25to40 400 2tabletsofthe200mg
Above40 600 Itabletof600mgtablet
ForchildrenonaPI-basedregimenwhorequiresuper-boostingofRitonavir,thedosingusedforRitonavirisasshownintable25.
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Table 25:Ritonavir Dosing for Super-Boosting LPV/r in Children Taking Rifampicin
Weight Range (kg) Lopinavir/ritonavir (LPV/r) Additional dosing of ritonavir for children
taking rifampin
Twice Daily Twice Daily Twice Daily
Lopinavir/ ritonavir 80/20mg/ml solution
Lopinavir/ ritonavir 200/50mg tablets
Ritonavir liquid (80mg/ml, in 90 ml bottle) Ritonavirdoseisadjustedtonearestmarkfortheeaseofmeasurement
3-5.9 1ml - 1ml
6-9.9 1.5ml - 1ml
10-14.9 2ml - 1.5ml
14-19.9 2.5ml 1tabtwicedaily 2ml
20-24.9 3ml 1tabtwicedaily 2.5ml
25-34.9 4ml 2tabinam&1tabin pm
4mlinam&2mlinpm
5.6 Cotrimoxazole Preventive Therapy (CPT)
CotrimoxazolehasbeenshowntoreducemortalityamongchildreninfectedwithHIV.AllTB/HIVco-infectedchildrenshouldbeofferedCPTanditshouldbestartedassoonaspossible.Thedurationoftreatmentisusuallylife-longwithaoncedailydosing.Thechildrenshouldbemonitoredforsideeffects,whichincludeskinrashesandgastrointestinaldisturbances.Severeadversereactionsareuncommonandusuallyincludeextensiveexfoliativerash,StevenJohnsonsyndromeorsevereanemia/pancytopenia.CPTshouldbediscontinuedifachilddevelopssevere adverse reactions. The recommended dosage of Cotrimoxazole forchildrenisshownintable26.
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Table 26: Recommended doses for Cotrimoxazole
Weightin Kg
Child Suspension(200mg/40mg per 5ml)
Child Tablet(100mg/20mg)
Single strengthadult tablet (400mg/80mg)
Double strengthadult tablet (800mg/160mg)
<5 2.5ml Onetablet ¼ tablet -
5-15 5ml Twotablets ½ tablet -
15-30 10ml Fourtablets Onetablet ½ tablet
>30 - - Twotablets Onetablet
• WhenDapsone(asasubstituteforCPT)isbeingusedasPCPprophylaxis,it isonly recommended forpatients inWHOStage4and/orabsoluteCD4count<200cells/mm3(orCD4%<25%forchildren≤5yearsold),and shouldbediscontinuedonce apatient achieves a sustainedCD4countof>200cell/mm3(or>25%forchildren≤5yearsold)foratleast6months.Itisgivenat2mg / kg once daily (maximum dose 100mg). It issuppliedin25mgand50mgtablets.
5.7 Immune re-constitution inflammatory syndrome (IRIS)
IRIS is a paradoxical deterioration after initial improvement following ARTtreatment initiation. It is seen during the initial weeks of TB treatmentwith initialworseningof symptomsdue to immune re-constitution. IRIS iscommonlyseen in theseverely immuno-compromisedTB/HIVco- infectedchildafterinitiatingARVtreatment.
IRISismanagedbycontinuinganti-TBtherapyandgivingnon-steroidalanti-inflammatorydrugsuntil severesymptomssubside.Prednisone isgivenat2mg/kg oncedailyfor4weeks,andthentaperdownover2weeks(1mg/kg for 7days, then 0.5mg/kg for 7 days then stop).
5.8 Prevention of TB in HIV
AllHIV-infectedchildrenneedtobescreenedforTB.AllHIVinfectedchildrenexposedtosputumsmearpositiveTBcaseshouldbeevaluatedforTBandtreated ifdiagnosedwithTBdisease.ThosewithoutTBdisease shouldbeofferedIsoniazidpreventivetherapyat10mg/kg/dayfor6months.
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All TB infected children should be offered counselling and testing for HIVinfection. KnownHIV infected children shouldminimize their exposure tootherpatientswithchroniccough(e.g.separatewaitingarea,orfasttracktheirconsultationfromthewaitingarea).
Thespecificneedsofeachfamilyshouldbedeterminedandaplanofactiondevelopedtoensurethatthefamilyreceivescomprehensivecareusingallavailableservices.Deliberateefforts shouldbemade toexpand thepreventionofmother tochildtransmission.This isbecauseminimizingHIVinfectioninchildrenwillreducetheirrisksofdevelopingTB.
BCGvaccineistobegiventoallnewbornbabiesexceptthosewithsymptomsofsevereHIVinfection.ItisalsonotgiventochildrenstartedonIPTbeforeitsadministration.InthesechildrencompletetheIPTcourseandwait2weeksafterIPTcompletiontogiveBCG.Always examine the placenta for tubercles because their presence mayimplicateverticalTBtransmission.
5.9 IPT in HIV infected children
ChildrenlivingwithHIVwhoaremorethan12monthsofage,whoareunlikelytohaveactiveTBonsymptom-basedscreeningandhavenocontactwithaTBcaseshouldreceivesixmonthsofIPTat10 mg/kg/ day (maximum300mg/day) aspartofacomprehensivepackageofHIVpreventionandcareservices.
InchildrenlivingwithHIVwhoarelessthan12monthsofage,onlythosewhohavecontactwithaTBcase,andwhoareevaluatedforTBshouldreceivesixmonthsofIPTiftheevaluationshowsnoTBdisease.Refertotable34forthedosageofIsoniazid(IPT)andtable13forthedosageofpyridoxineinchildren.
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CHAPTER 6
TB in special circumstances
6.1 Management of a baby born to a Mother with PTB
CongenitalTBisTBacquiredin-uterothroughhaematogenousspreadviatheumbilicalvessels,oratthetimeofdeliverythroughaspirationoringestionofinfectedamnioticfluidorcervico-vaginalsecretions.CongenitalTBusuallypresentsinthefirst3weeksoflifeandmortalityishigh.
NeonatalTBisTBacquiredafterbirththroughexposuretoaninfectiouscaseofTB-usuallythemotherbutsometimesanotherclosecontact.ItisoftendifficulttodistinguishbetweencongenitalandneonatalTBbutmanagementisthesameforboth.TransmissionofTBwithinnewbornunits,paediatricwardsandmaternitywardsdoesoccurinovercrowdedhealthfacilities,hencetheneedtoimplementinfectionpreventioncontrolmeasures(includingtheuseofsurgicalmasks)wheneveronecaseofTBhasbeenidentifiedwithinthissetup.Thisistoreducetransmissiontonew-bornswhoareextremelyvulnerabletoTB.
TheTB-exposedneonate ishighlyvulnerableandmayrapidlyprogress tosymptomaticandsevereTBdisease.SymptomsandclinicalsignsofneonatalTBareusuallynonspecificandexamplesareshownintable28.
Table 28: Signs and symptoms of neonatal TB
Symptoms Clinical signs
Lethargy Respiratorydistress
Fever Non-resolving‘pneumonia’orrespiratoryinfection
Poorfeeding Hepatosplenomegaly
Lowbirthweight Lymphadenopathy
Poorweightgain Abdominaldistension
Clinicalpictureof‘neonatalsepsis’
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ThediagnosisofTBshouldbeincludedinthedifferentialdiagnosisofachildwith neonatal sepsis, poor response to antimicrobial therapy, congenitalinfectionsandatypicalpneumonia.ThemostimportantcluetothediagnosisofneonatalTBisamaternalhistoryofTBoranycontactwithapersonwithchroniccough.
Always examine the placenta for tubercles because their presence mayimplicateverticalTBtransmission.
6.2 Management of the asymptomatic neonate exposed to maternal TB
IfaneonateisborntoamotherwithTB,orisexposedtoaclosecontactwithTB,IsoniazidPreventiveTherapy(IPT)shouldbegivenfor6monthsonceTBdiseasehasbeenruledout.2weeksaftercompletionofIPT,giveBCG.Itisnotnecessarytoseparatetheneonatefromthemother.However,themothershouldbeeducatedoninfectionpreventioncontrolmeasures.
Breastfeeding is not contraindicated for a child whose mother has TB
Neonates born to mothers with MDR-TB or XDR-TB should however bereferredforTBscreeningandmanagement.IPT should not be given.InfectioncontrolmeasuressuchasthemotherwearingamaskarerequiredtoreducethelikelihoodofmothertochildtransmissionofDRTB.
6.3 Management of the neonate with TB disease
IfaneonatewhoisexposedtoamotheroranothercontactwithTBisfoundtohavesymptomssuggestiveofTB,treatmentwithanti-TBsshouldbeinitiatedevenwhileawaitingbacteriologicalconfirmationasTBprogressesrapidlyinneonates.Drugdosagesmustbetailormadebasedontheneonate’sweight.Refer to table 10 in chapter 4.Breastfeedingisencouraged.
6.4 TB among children in congregate settings
Children may contract TB in congregate settings outside the household.Thesecongregatesettingsincludechildcare(daycare)centres,orphanages,prisons(juvenileprisons),(dayandboarding)andrefugeecamps.Thisisdue
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to several factors includingovercrowding, poor handhygiene, poor coughetiquette,poorventilation,andgeneralpoorTBinfectioncontrolmeasuresinplace.
OnceachildhasbeendiagnosedwithTBwithinthecongregatesetup,alleffortsmust bemade to screen all contacts of the diagnosed child,whileconductingreversecontacttracingtoidentifytheindexcase.AllpresumptiveTB cases must be evaluated according to the algorithm for TB diagnosisandthosediagnosedwithTBinitiatedontreatment.Wherefeasible,olderchildrenwithbacteriologicallyconfirmedTBwithinthesecongregatesettingsshouldbeseparatedorisolatedfromothersuntiltheyareconsideredatlowriskfortransmission(aftersputumconversion).
Congregate settings are an important component of the country’s TBsurveillanceactivitiesandshouldbeassessedforTBinfectioncontrol.Suchassessments should be followed by screening of all presumptive TB casesand development of infection prevention and control plans to supportadministrative,environmentalandrespiratorymeasures.
6.5 TB/DM co-morbidity
Changesinlifestyleanddiethavecontributedtoanincreasedprevalenceofdiabetesinlowandmiddle-incomecountrieswheretheburdenofTBishigh.ThegrowingburdenofdiabetesiscontributingtosustainedhighlevelsofTBin thecommunity,andtheproportionofTBcasesattributable todiabetesglobally is likely to increaseovertime. This double burdenof disease is aseriousandgrowingchallengeforhealthsystems.Diabetescanworsentheclinical courseof TB, andTB canworsenglycaemic control inpeoplewithdiabetes.Childrenwithbothconditionsrequirecarefulclinicalmanagementensuringoptimalcareisprovidedforbothdiseases.
Symptomsofdiabetesincludeexcessiveexcretionofurine(polyuria),thirst(polydipsia),constanthunger,weightloss,visionchangesandfatigue.Thesesymptomsmayoccursuddenlyorinsidiously.
Type 1 diabetes (previously known as insulin-dependent, juvenile orchildhood-onset)ischaracterizedbydeficientinsulinproductionandrequiresdailyadministrationofinsulin.Thecauseoftype1diabetesisnotknownanditisnotpreventable.
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Type 2 diabetes (formerly called non-insulin-dependent or adult-onset)resultsfromthebody’sineffectiveuseofinsulin.Type2diabetescomprises90%ofpeoplewithdiabetesaroundtheworld,and is largelytheresultofexcessbodyweightandphysical inactivity.Symptomsmaybe likethoseofType1diabetes,butareoftenlessmarked.Asaresult,thediseasemaybediagnosedseveralyearsafteronset,oncecomplicationshavealreadyarisen.Until recently, type 2 diabeteswas seen only in adults but it is now alsooccurringinchildren.
AlldiabeticchildrenshouldbescreenedforTBateveryclinicalvisitandtheresultsrecordedintheirdiabeticcarerecords.AlldiabeticchildrenwithTBshould be started on anti TB treatment immediately and their glycaemiccontrolmonitoredclosely.
TBinfectioncontrolshouldbeensuredinareaswherediabetesismanaged.Administrativemeasuresincludeearlyrecognition,diagnosisandtreatmentofTB.Duringdiabetesclinicvisits,childrenwithTBanddiabetescanbeseenonadifferentdayoratadifferenttimetoreducetheriskofTBtransmissiontootherchildren.
Eachhealth-carefacilityshouldhaveaninfectioncontrolplan,whichincludesadministrativeandenvironmentalcontrolmeasurestoreducetransmissionofTBwithinthissetting.ThesemeasuresshouldadheretoNationalGuidelinesforTBinfectionControl.
All children with both TB and Diabetes should receive pyridoxine for thedurationofTBtreatmenttoreducetheriskofperipheralneuropathy.Ifthechild is on DR TB treatment with aminoglycosides, there should be closemonitoringoftherenalfunctions.Inrenalimpairment,thedoseofanti-TBsshouldbeadjusteddownwardsaccordingtothecreatinineclearance.RenalfunctiontestshouldbedonemonthlyforDRTB/Diabetespatients.Glycaemiccontrol needs to be closelymonitored in underweight co-morbid patientswhowouldneedanincreasedcaloricintakeandtheirdoseofinsulinadjustedaccordingly.Thesepatientsarebestmanagedbya teamthat includes thenutritionist.
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6.6 TB among street families
In 2007, the Consortium of Street Children estimated that there were250,000-300,000childrenlivingandworkingonthestreetsofKenyawith,morethan60,000ofthemlivinginNairobi.ThepopulationofstreetfamiliesinKenyaisquitefluid.
StreetfamilieshaveseveralfactorsthatputthematahigherriskofcontractingTBincluding;
• Malnutrition• Sexual exploitation accompaniedby a high risk of contracting STIs
andHIV/AIDS• Illicitdruguse• Smoking• Poorhygienicandsanitaryconditions• Pooraccesstohealthcare
Persons living on the streets experience longer delays in accessingcomprehensive healthcare due to social exclusion and inmost cases, willaccess healthcare quite late in the disease process. During this period,transmissionmayoccuramongstgroupsofstreetfamiliesandthehomeless.Poorcomplianceresultsinloweffectivenessofanti-TBsandanincreasedriskofDRTB.MalnutritioncontributestohigherTBmortalityinthisgroup.
Street children with TB require close follow up and attachment to socialworkersorchildren’s’homes.ItispreferabletogiveDOTsforthoseabletovisithealthfacilitiesdaily,whiletailormadesolutionsforcompliancemustbediscussedtoensurethesechildrenareabletotaketheirdrugsasrequired,particularlyiftheirfamiliesmovefromplacetoplace.Outreachmissionsarea resource inmobilizing street families for screening andprovidinghealtheducationtothem.
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CHAPTER 7
Drug Resistant TB
Drug resistant (DR) TB occurs when Mycobacterium tuberculosis bacilliare not killed or inhibited by Anti-tuberculosis drugs that they have beensubjected to. This results in selection of acquired or naturally occurringresistant mutants.
• Primary drug resistanceoccurswhenthepatientisinfectedwitharesistancestrainofmycobacteriumtuberculosis
• Acquired or Secondary resistanceoccurswhenthepatientisinfectedwith a drug susceptible strainwhichbecomes resistant overtime.Itisclinicallymanifestedbydiseaseprogressiondespitetreatment,failuretoachievesputumorculturesconversion
Inchildren, it ismainly the resultof transmissionofDRTBbacilli fromaninfected source. It should be highly suspected in a child with history ofexposuretoaknownDRTBcaseortoapersonwithachroniccough.
ResistancetoRifampicinand/orIsoniazidisthemostimportant,asthesetwodrugsformthebackboneofthecurrentTBchemotherapy.
7.1 Classification of drug resistant TB
Drugresistanceisclassifiedasshownintable29.
Table 29: Classification of drug resistant TBMono-resistant TB Resistancetoonefirstlineanti-TBmedicineonly
Poly-resistant TB ResistancetomorethanonefirstlineantiTBmedicineotherthanbothRifampicinandIsoniazid
Rifampicin Resistant (RR) ResistancetoatleastRifampicininabsenceofIsoniazid(INH)resistance
Multi-drug resistant (MDR) TB Resistance to both Isoniazid and Rifampicin with or without othermedicines(excludinginjectablesandquinolones)
Pre–XDR TB ResistancetoIsoniazidandRifampicinandeitherafluoroquinoloneorsecond-lineinjectableagentbutnotboth
Extensive drug resistant (XDR) TB ResistancetoRifampicin,Isoniazid,aninjectableandaquinolone
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Presumptive drug resistant TB cases:These are patients without bacteriological confirmation but are highlysuspectedtohavedrugresistantTB.Theseinclude:
• PresumptiveMDRTB,• PresumptiveXDRTB• PresumptiveRifampicinresistantcases.
7.2 Diagnosis
Drug-resistantTBshouldbesuspectedwhen:• ThereiscontactwithknownDR-TB• ThereiscontactwithsuspectedDR-TB,i.e.sourcecasehadtreatment
failureorwaspreviouslytreated• A child with TB is not responding to first-line therapy despite
adherence• AchildpreviouslytreatedforTBpresentswithrecurrenceofdisease
WhenDR-TBissuspected,everyeffortshouldbemadetoconfirmthediagnosisbyobtainingspecimensforcultureanddrugsusceptibilitytesting(DST).RapidDSTof IsoniazidandRifampicinorRifampicinalone is recommendedoverconventionaltestingornotestingatthetimeofdiagnosis.ChildrenwithoutbacteriologicalconfirmationbutarehighlysuspectedtohavedrugresistantTBshouldbeinitiatedonDRTBtreatment.
ForchildrenwhoareconfirmedcontactsofanindexcaseofDRTB,treatasperresistancepatternoftheindexcaseinabsenceofdrugsensitivitytestingconfirmation.AdjusttreatmentregimenbasedonDSTresults.
ThediagnosisofchildrensuspectedtohaveMDRTBisassummarizedinthealgorithmasshowninfigure8.
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Figure 8: Diagnostic algorithm for the diagnosis of DR-TB in childrena
aThis is produced from Schaaf HS, Marais BJ. Management of multidrug-resistant tuberculosis in children: a survival guide for paediatricians.Paediatric Respiratory Reviews,2011,12:31-38aspresentedintheGuidancefor national tuberculosis programs on themanagement of tuberculosis inchildren(secondedition)
7.3 Treatment of DR TB in children
Thetreatmentvarieswiththeresistancepatternasperthetablebelow:Basic principles of treatment of DR TB:
• Donotaddadrugtoafailingregimen• WhiletreatingachildwithpresumptiveDRTB,usetheregimenof
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theindexcaseandadjustoncethechild’sDSTresultsareavailable• Useatleastfourdrugstobeeffective• PyrazinamideisincludedaspartoftheMDRTBregimen• DopatientbaselinetestspriortotreatmentasperthePMDTguidelines.
Delayinbaselinetestresultsshouldnotdelaytreatmentinitiation.• Getthecaregivertosignacommitmenttoadheretotreatmentonce
theyhavebeeneducatedaboutDRTB• Usedailydirectlyobservedtherapy(DOT)only• Counselthechild’scaregiverateveryvisittoprovidesupport,advice
about adverse events and the importance of compliance andcompletionoftreatment
• Dosingfortreatmentshouldbebasedonthechild’sweight.Adjustthedosewheneverthechild’sweightchanges
TherearedifferentpatternsofdrugresistantTB.Thesevarydependingonthenumberofdrugsachild is resistant to.Treatmentalsovarieswith thedifferentresistancepatternstoTBtreatmentasshowninthetable30.
Table 30: Patterns of drug resistance and recommended treatment
Pattern of drug resistance Regimen Duration of
treatment
Mono Resistant H(±S) R/Z/E/LFX 9Months
Poly Drug Resistant
H,E,Z(±S) 3Cm-Lfx-R-Z/15Lfx-R-Z** 18Months
HandZ 3Cm-Lfx-R-Z/15Lfx-R-Z** 18Months
HandE 3Cm-Lfx-R-Z/15-Lfx-R--Z** 18months
MDR TB R & H (MDR TB) 8Cm-Pto-Lfx-Cs-Z / 12 Pto-Lfx-Cs-Z* 20 months
RR TB
R 8Cm-Pto-Lfx-Cs-Z/12Pto-Lfx-Cs-Z* 20months
RandE(±S) 8Cm-Pto-Lfx-Cs-Z/12Pto-Lfx-Cs-Z* 20months
RandZ(±S) 8Cm-Pto-Lfx-Cs-Z/12Pto-Lfx-Cs-Z* 20months
H-Isoniazid R-Rifampicin E-Ethambutol S-Streptomycin LFX-LevofloxacinCs-Cycloserine Pto-ProthionamideCm-CapreomycinZ-Pyrazinamide
*AsampleshouldbecollectedforcultureandDSTandthepatientstartedonMDRregimen
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**Considerapatient’spreviousTBdrughistorybetweenthetimeofsamplecollection and results being received before starting the patient on therecommendedregimen.Thedosage andmechanismof actions for the variousmedicines used forMDRTBtreatmentisasshownintable31.
Table 31: Second-line anti-TB drugs for treatment of MDR*-TB in children
Medication Dose Maximum daily dose
Isoniazid(H) 10mg/kgdaily 300mg
Rifampicin(R) 15mg/kgdaily 600mg
Ethambutol(E) 25mg/kgdaily 1200mg
Pyrazinamide(Z) 30-40mg/kgdaily 1500mg
Streptomycin(S) 20-40mg/kgdaily 1000mg
Kanamycin(K) 15-30mg/kgdaily 1000mg
Capreomycin(Km) 15-30mg/kgdaily 1000mg
Ofloxacin(Ofx) 15-20mg/kgdaily 800mg
Levofloxacin(Lfx) 15-25mg/kgdaily 1000mg
Moxifloxacin(Mfx) 7.5-106mg/kgdaily 400mg
Ethionamide(Eto) 15–20mg/kgdaily 1000mg
Cycloserine(Cs) 10–20mg/kgdaily 1000mg
Terizidone(Trd) 10–20mg/kgdaily 1000mg
Para–aminosalisylicacid(PAS) 150mg/kgdaily 8g(PASER)
* MDR: multidrug resistantAlthough Fluoroquinolone are not approved for use in children in mostcountries,thebenefitoftreatingchildrenwithMDR-TBwithaFluoroquinolonemayoutweightheriskinmanyinstances.
7.4 Extensive Drug resistant TB (XDR TB)Treatmentregimenistailoreddependingonresistancepattern.AllchildrenwithsuspectedorconfirmedXDRTBshouldbereferredtoaspecialist/clinicalcommitteeforfurtherevaluationandmanagement.
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7.5 Follow up for DR TB treatment• AllattemptsshouldbemadetogetmycobacterialcultureandDST
during treatment for any childwho did not have bacteriologicallyconfirmedDRTBdiseaseatdiagnosis
• Clinical, radiological and bacteriological mycobacterial culture foranychildwhohadbacteriologicallyconfirmeddiseaseatdiagnosisisessential
• Patientontreatmentshouldbemonitoredmonthlyusingclinicalandlaboratoryevaluationaspertheguideintable32.
Table 32: Patient monitoring schedule for patients with MDR TBMonth Baseline 1 2 3 4 5 6 7 8 9 10 11 12 15 18 21
Clinicalreview X
Every2 weeks
X X X X X X X X X X X X X X
Audiometry X X X X X X X X X
Weight X X X X X X X X X X X X X X X X
Height X X X X X X X X X X X X X X X X
Smear X X X X X X X X X X X X XMonthlytilltreatment completion
Culture X X X X X X X X X X X X XMonthlytilltreatment completion
DST X SLDDST
LFTs(AST,ALT,Bilirubin) X X X X X X X X X
Creatinine,Potassium X X X X X X X X X
Fullhemogram X X X X X
CD4 X
ViralLoad X X X
CXR X X X X
TSH X X X X X
Pregnancytest X
Note• SecondlineDSTshouldbedoneatthebeginningoftreatmentandcarriedoutifa
culturenegativepatientturnspositive• Liver function and kidney function tests may be done at any time as clinically
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indicated• Patient’sheightshouldbetakenatbaselineinadultsandmonthlyinchildren.BMI/
Z-scoreshouldbecalculatedmonthly• Thepatient’sHIVtestshouldbedoneatbaselineandrepeatedaspertheguideline• Hemogram(HB)inapatientonZidovudine(AZT)shouldbecarriedoutatbaseline,
4,8and12months
7.6 Side effects for second-line treatment and management
With correct dosing, few long-term side effects are seen even with themore toxic second line drugs in children, including Ethionamide andFluoroquinolone.Someofthecommonsideeffectsandtheirlikelycausativeagentsisasshownintable33.
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Table 33: Common side effects of second-line medicines, their likely causing agents, and suggested management strategies
Classification group Name of Drug
Side-effects
Common Uncommon
Group 1: First-line oral anti-TB agents
Isoniazid (H) Hepatitis, Cutaneous hypersensitivity, Peripheral neuropathy
Giddiness, Convulsion, Optic neuritis, Mental symptoms, Haemolytic anaemia, Aplastic anaemia, Lupoid reactions, Arthralgia, Gynaecomastia
Rifampicin (R)
Hepatitis, Cutaneous hypersensitivity, Gastrointestinal reactions, Thrombocytopenic, purpura, Febrile reactions, “Flu syndrome”
Shortness of breath, Shock, Haemolytic anaemia, Acute renal failure
Ethambutol (E) Retrobulbar neuritis, Arthralgia Cutaneous reaction, Peripheral neuropathy
Pyrazinamide (Z) Hepatitis, Nausea, Vomiting, Arthralgia, Sideroblastic anaemia
Group 2: Injectable anti-TB agents
Streptomycin (S)Cutaneous hypersensitivity, Giddiness, Numbness, Tinnitus, Vertigo, Ataxia, Deafness
Renal damage, Aplastic anaemia
Kanamycin (Km)Ototoxicity: hearing damage, vestibular, disturbance, Nephrotoxicity: deranged renal function test
Clinical renal failure
Amikacin (Am)Ototoxicity: hearing damage, vestibular, disturbance, Nephrotoxicity: deranged renal function test
Clinical renal failure
Capreomycin (Cm)Ototoxicity: hearing damage, vestibular, disturbance, Nephrotoxicity: deranged renal function test
Clinical renal failure
Group 3: Fluo-roquinolones
Ofloxacin (Ofx) Gastrointestinal reactions, Insomnia Anxiety, Dizziness, Headache, Tremor, Convulsion
Levofloxacin (Lfx) Gastrointestinal reactions, Insomnia Anxiety, Dizziness, Headache, Tremor, Convulsion
Moxifloxacin (Mfx) Gastrointestinal reactions, Insomnia Dizziness, Restlessness, Diarrhoea
Group 4: Oral Bacteriostatic 2nd line anti-TB agents
Ethionamide (Eto) Gastrointestinal reactions Hepatitis, Cutaneous reactions, Peripheral neuropathy
Prothionamide (Pto) Gastrointestinal reactions Hepatitis, Cutaneous reactions, Peripheral neuropathy
Cycloserine (Cs) Dizziness, Headache, Depression, Memory loss Psychosis, Convulsion
P-aminosalicylic acid (PAS) Gastrointestinal reactions Hepatitis, Drug fever, Hypothyroidism,
Haematological
Terizidone Dizziness, Headache, Depression, Memory loss Psychosis, Convulsion
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CHAPTER 8
Prevention of TB
8.1 Infection prevention and control
Tuberculosisinfectionpreventionandcontrol(IPC)referstoacombinationofmeasuresaimedatminimizingtheriskofTBtransmissionwithinpopulations.It complements core interventions in TB and HIV control. It is importantbecauseof:
• AssociationofTBwithHIV• EmergenceofdrugresistantTB(DR-TB)• IncreasedriskoftransmissionamongcontactsofTBpatients,health
carefacilitiesandcongregatesettings
Patientscaninfectotherpatients,workers,orvisitors.Likewise,workerscaninfectpatients,otherstafforvisitorsandvisitorscaninfectpatients,workersandothervisitors.
IPC measuresThere are three levels of IPC measures:1. Administrativecontrolmeasures2. Environmentalcontrolmeasures3. Personalprotectiveequipment
1. Administrative control measures ThesearedefinedasthemanagerialorworkpracticesthatreducetheriskofTBtransmissionbypreventingthegenerationofdropletnucleiandlimitingexposuretodropletnuclei.
AdministrativesupportforTBinfectioncontrolinvolves:• Administrative commitment to implementation of TB infection
control is necessary within facilities to ensure success of TBpreventionefforts
• An Infection Prevention and Control Committee: Itshouldbeformedtocoordinateactivitiesamongstdifferentfacilityservices
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Therearethreekeycomponentsofadministrativecontrols.Theseare:1. TB Infection Prevention and Control assessment.Thisentails:• ReviewofthestatisticalTBreports• EvaluationofexistingTBIPCactivities• Identificationandprioritizationof themost-at-risk settings
withinthefacility• IdentificationofcategoriesofHCWsthatneedtobeincluded
inaTBscreeningprogram• Identification of mechanisms for prompt recognition and
reportingofpresumptiveTBepisodesandTBtransmission
2. Patient managementThefollowingarethekeystrategiesofpatientmanagementtopreventTBtransmission:• Screeningofclientsforcoughastheyenterthefacility• Educationofclientsoncoughhygiene• Provisionofmasks/tissuestocoughingclientsastheyenter
thefacility• Separationofclientswhocoughfromthosewhodon’t• Reductionofwaitingtimesforclientswhocough• Earlyreferraland investigationofclientswhoarecoughing
forTB• Provisionofasafeenvironmentforcollectionofsputum• Reducingexposureinthelaboratory• Isolation• SurveillanceforTBdisease/infectionamongHCW
3. Development of an infection control planDevelopmentofanIPCplanwillbebasedonthefollowing:• Riskassessmentresults• TBsurveillancedata• EpidemiologicaldataTheIPCplanshouldbemonitoredmonthlyandevaluatedeveryyear.Theplanshouldinclude:• DescriptionoftheincidenceorTBandTB/HIVinthefacility• AssessmentofHCWtrainingneedsandtrainingplan• Administrative policies regarding triage and screening,
referralanddiagnosis,separationandisolation
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• Usingandmaintainingenvironmentalcontrols• Policyonthetraininganduseofrespiratoryprotection• Area-specificinfectioncontrolrecommendations• Descriptionofrolesandresponsibilitiesforimplementation
andmonitoringtheinfectioncontrolplan• Time-lineandbudget(e.g.,materialandpersonnelcosts)
2. Environmental control measuresThesearemeasures thatareused to reduce the concentration of droplet nuclei in the air.Suchmeasuresincludemaximizingnaturalventilationandcontrollingthedirectionofairflow.Therearetwotypesofenvironmentalcontrols:
1. Natural ventilationSimple natural ventilation may be optimized by maximizing the size oftheopeningofwindowsanddoorsand locating themonopposingwalls.Where possible, the use of natural ventilation should be maximized before considering other ventilation systems.
2. Mechanical ventilationWell-designed, maintained and operated fans (mixed-mode ventilation)canhelptoobtainadequatedilutionwhennaturalventilationalonecannotprovidesufficientventilationrates.Personal protective equipment This refers to items specifically used to protect the health care provider,thepatientandthecommunityfromexposuretobodilydischargesorfromdroplet or airborne organisms. Personal protective equipment includesgloves,aprons,gowns,caps,surgicalmasks, respiratorsandprotectiveeyegear.
N95 for health care workers
• N95areaspecialtypeofrespiratorsthatprovide94-95%filtrationefficiencyagainst0.3-0.4micrometreparticles
• Theyshouldbecloselyfittedtothefacetopreventleakagearoundtheedges.Iftherespiratorisnotworncorrectly,infectiousdropletnucleicaneasilyenteraperson’sairways,potentially resulting ininfection. The N95 masks can be re-used repeatedly for severalweeksiftheyareproperlystoredbeforedisposal
• Respirator should be stored in a clean dry location devoid ofhumidity,dirtandfilterdamage
• Plasticbagsshouldneverbeusedsincetheyretainhumidity
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Protection in high risk areas• Respiratorsshouldbewornbyallpersonnelenteringhighriskareas
such as bronchoscopy rooms, sputum induction rooms,MDR-TBisolationwards,peoplehandlingspecimensinthelaboratory,MDR-TBClinic
• The use of powered air- purifying respirator (PAPR) is alsorecommendedwherehighriskproceduresareperformed,fortheyarecost-effectiveandarere-usableanddoesnotrequirefittesting
Note:It is important to remember that a surgicalmaskwornbyHCWsmaynotadequately protect them from inhalation of air contaminated with M.tuberculosis.RespiratorsarethepreferreddevicetoreducetheconcentrationofM.tuberculosisbacilliinhaled.
Multi-Drug Resistant and Extensively Drug Resistant TBThehealthcareworkersworkingwithDRTBpatientsshouldtakenecessarypreventiveprecautions.Theseinclude:
1. EducatingthecommunityaboutTBinfectionpreventionandcontrol2. Sensitizing MDR-TB care providers at community level on risk of
transmissionandprovidingthemwithbasicprotectiveequipment3. ProvidingMDR-TBpatientswithbasicpersonalprotectiveequipment
(surgical mask) for use in the home setting where there arevulnerablegroupslikechildrenunderfiveyearsofage,theelderlyandchronicillpeople
8.2 Screening for Child Contacts of known TB Cases
Youngchildren living inclosecontactwithan indexcaseofsmearpositivepulmonaryTBareatahighriskofTBinfectionanddisease.Theriskofinfectionisgreatestif:
• Thecontactiscloseandprolonged• Thechildismalnourishedchildren• Thechildisunder5years• ThechildisHIVinfected
Diseaseusuallydevelopswithin2yearsofinfection.Ininfants,thetimelagcanbeasshortasafewweeks.
IsoniazidPreventiveTherapy(IPT)foryoungchildren(agedlessthan5years)exposedtoTBwhohavenotyetdevelopeddiseasewillgreatlyreducethelikelihoodofdevelopingTBduringchildhood.
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Contact screening refers to the evaluation for TB of all children who are close contacts of bacteriologically
confirmed PTB casesReverse contact screening refers to the evaluation of all
possible source cases of a child diagnosed with TB disease
Themainpurposeofchildcontactscreeningisto:1.Identifysymptomaticchildren(i.e.childrenofanyagewithundiagnosedTBdisease)andtreatthemforTB.
2.ProvideIsoniazidPreventiveTherapy(IPT)forthehigh-riskchildrenwhohavenosignsorsymptomsofTBdisease.
Process of contact investigation (CI)WhenCIisinitiatedtheindexcaseshouldbeinterviewedassoonaspossibleafter the diagnosis (generally within one week) to elicit the names ofhouseholdmembersandotherclosecontacts.
Thefocusshouldbeonhouseholdmembers,wheretheyieldispotentiallyhighest,butworkplaceandsocialcontactsshouldnotbeignored.
If thehumanresourcesareavailable, thepersonconductingtheCIshouldvisitthehomeoftheindexpatienttoensurethatallcontactsareinterviewedand referred for evaluation when indicated. This is usually done by thecommunityvolunteerorattimesthehealthcareworker.Thevisitwillgiveamoreaccurateviewoftheactualcircumstancesoftheexposureandprovideanopportunityforidentificationofneededsocialsupport,andforeducationregardingtuberculosisandinfectioncontrolmeasuresthatmaybetaken.
Ifachildpresentswithactivetuberculosis,itisimportanttoconductwhatisoftenreferredtoas“reversecontacttracing.”Mostsickchildrencontractedtuberculosisfromanadultwiththediseasewithwhomtheyhavehadclosecontact.Withreversecontacttracing,attemptsaremadetoidentifytheadultwhoisthesourceoftheinfection.
Data onCI should be collected in the recommended contact tracing toolsavailedbytheTBprogram.
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ContactscreeningisdoneusingasymptomscreenusingthesetofquestionsaslistedintheICFtool.Theseinclude:1.Cough2. Fever 3.Lossofweight/poorweightgain4.Lethargy/malaise/reducedplay5.Extrapulmonarysignsandsymptomse.g.enlargedcervicalLN
AchildorcontactthathasanyofthesignsandsymptomsofTBshouldbereferredtothenearesthealthfacilitytohaveafullevaluationforTB.
ContactsfoundtohaveTBdiseaseareinitiatedonthefullcourseoftreatmentwhilethosewithoutTBarecounselledtoidentifysignsandsymptomsandadvisedwhentoreturn.Contactsagedlessthan5yearstheyareinitiatedonIPTonceTBdiseasehasbeenruledout.
Managementofchildcontactsissummarizedinthealgorithminfigure9.
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Figure 9: Management of a Child who has been exposed to an adolescent or adult with Pulmonary TB
8.3 IPT in HIV infected children
IsoniazidisusedforpreventionofTB.Itisgivenatadoseof10mg/kgforover6monthsinchildren.BeforegivingIPT,TBdiseaseshouldberuledout.All
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childrenonIPTshouldreceivepyridoxineatrecommendeddoseasintable13.
ChildreneligibleforIPTinclude:• ChildrenlivingwithHIVwhoaremorethan12monthsofage,who
areunlikelytohaveactiveTBonsymptom-basedscreeningandhavenocontactwithaTBcaseshouldreceivesixmonthsofIPTat10 mg/kg/ day(maximum300mg/day)
• InchildrenlivingwithHIVwhoarelessthan12monthsofage,onlythosewhohavecontactwithaTBcase,andwhoareevaluatedforTBshould receivesixmonthsof IPT if theevaluationshowsnoTBdisease.
• Allchildrenunder5yearsofagewhohavebeenexposedtoacaseofinfectiousTBirrespectiveoftheirHIVstatusshouldbeputonIPTifTBdiseasehasbeenruledout.
Table 34: Dose of Isoniazid (INH) for Isoniazid Preventive Therapy (IPT) in children
Weight (kg) Daily Dose in mg Number of 100 mg, INH tablets
2 – 3.4 25 1/4
5.1 – 9.9 100 1
10-14.9 150 1½
15-19.9 200 2
20-29.9 300 3*
*Forchildrenmorethan20kg,onecanuse1adult tabletof INH(300mg)oncedaily.
All children on IPT should also receive pyridoxine.
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8.4 BCG Vaccination in Children
BCG isa liveattenuatedvaccinederived fromM bovis. ItoffersprotectionagainstthemoreseveretypesofTBsuchasMilliaryTBandTBmeningitis,whicharecommoninyoungchildren.
A child who has not had routine neonatal BCG immunization and hassymptomsofadvancedHIVdisease(WHOStage3or4)shouldnotbegivenBCGbecauseoftheriskofdisseminatedBCGdisease.
In children with suspected TB infection or disease, the BCG vaccinationshouldbedeferredtill2weeksaftercompletionofIPT/TBtreatmentbecausetheanti-TBmedicineswilldenaturethevaccine.
Disseminated BCG diseaseAsmallnumberofchildren(1–2%)maydevelopcomplicationsfollowingBCGvaccination.Thesecommonlyinclude:
• Localabscessesattheinjectionsite• Secondarybacterialinfections• Suppurativeadenitisintheregionalaxillarylymphnode• Localkeloidformation.• Disseminated BCG disease. If axillary node enlargement is on the
samesideasBCGinaHIV-positiveinfant,considerBCGdiseaseandrefer.
Most reactionswill resolve spontaneously over a fewmonths and do notrequirespecifictreatment.ChildrenwhodevelopdisseminatedBCGdiseaseshouldbe investigated for immunodeficiencyand treated forTBusing thefirst-lineregimen:2RHZEthen4RH.Thechildshouldalwaysbereviewedbyaspecialist.
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CHAPTER 9
Roles and Responsibility
TBisacurableandpreventabledisease.Therefore,variousindividualsinthecommunityandhealthfacilitieshavearesponsibilitytopreventtransmissionand promote treatment adherence among patients, families and thecommunity at large. Health education is equally important for creatingawarenessaboutTB,changingattitudesandbehaviourandreducingstigmaanddiscrimination.
Theserolesaredefinedfromthelowestlevelofthepatientandcommunityunitstothehighestlevelofcare.Theselevelsofhealthcareare:
Level I-Communityunits(thisincludespatient,family,CommunityHealthVolunteer (CHV), Community Health Extension Worker (CHEW) andcommunity)Level II-DispensaryLevel III-HealthcentreLevel IV- PrimaryreferralunitLevel V-SecondaryreferralunitLevel VI-TertiaryreferralunitThe patient, family, CHV, CHEW and community
The patientEverypatienthasarighttoaccesshealthcare;wherehealthcareshallincludepromotive, preventive, curative, reproductive, rehabilitative and palliativecare. These responsibilities are borne by the children themselves (olderchildren)orbytheparentsorcaregivers(youngerchildren).Theyinclude:
• ToinformotherfamilymembersandpeopleinclosecontactwithtoundergoTBscreening
• Totakecareofhis/herhealthbyadoptingahealthylifestyle.TheTBpatientshouldspendmoretimeinanopenspacetoreduceindoortransmission
• Forchildren,protection,careandhealthylifestyleoftheminorshallbetheresponsibilityoftheirparentorguardian
• Toadoptapositiveattitudetowardstheirhealthandlifethathelpsthem to overcome stigma and discrimination. This will help themto take part in peer/support groups and help others to complete
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treatment• To respect the rights of others and not to endanger their life and
healthbycompletingtreatmentandobservingcoughetiquetteandhygiene
• To give health care providers relevant, accurate information tofacilitate diagnosis, treatment, rehabilitation and/or counsellingwhilebeingtruthfulandhonestonpasthealthcare.Inyoungchildren,parentsandcaregiversusuallydothis.Itisimportantforthehealthcareworkertoaskforhistoryofcontactwithadult/adolescentwithchroniccoughorTBwithinthelast2year
• Totakecareofthehealthrecordsinhisorherpossessionandproducethemwhenrequiredbythehealthcareprovider.ThisisnecessarytosupporthistorytakinginTB
• Tokeepscheduledclinicappointments• Tofollowinstructions,adheretoandnotabuseormisuseprescribed
medication or treatment and/or rehabilitation requirements. TBmedication requires consistency as non- adherence will lead tounfavourabletreatmentoutcomes
• Toseektreatmentattheearliestopportunity• ToexpressanyhealthconcernstotheHCW• Tobetreatedwithrespectandtheirhealthinformationtreatedwith
confidentiality
9.1 Family/ Household members
• Parents/caregiversshouldensurethatallnewbornbabiesaregivenBCGandotherprimaryvaccines
• Children,parents,andotherfamilymembersshouldseekinformationaboutTBandtheimportanceofcompletingtreatment
• Tosupportandobservethechildduringtreatmentaccordingtotheinstructionprovidedbythehealthcareworker
• Lactatingmotherswith children suffering from TB should practiceexclusivebreastfeedingforthefirst6months
• Providethechildwithahealthydiet• Provide a TB free environment by ensuring good ventilation and
observecoughhygieneandetiquette• TB patients who develop complications should be referred to an
expertforevaluationandtreatment
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9.2 The community:
• EnsureindividualswithsuggestivesymptomsofTBarescreenedandthoseontreatmentsupportedtoadheretotreatment
• MobilizepatientslosttofollowuptoresumetheirTBtreatment• CreateawarenessonTBtoreducestigmaanddiscrimination• Ensuringadequateventilationandminimizingcrowdingincongregate
settingslikeschools,prisons,childrenhomesetc.
9.3 Community Health Volunteers (CHVs)/ Community Health Extension Worker (CHEW)
CHVsaremajorplayers in the implementationofprimaryhealthcaresince1980s.Theyplayamajorroleinmobilizingcommunitiestotakecareoftheirhealthandprovidebasichealthcareatcommunitylevel.CHEWsplayaroleintrainingCHVsandprovidealinkagebetweenthecommunityandthehealthsystem.TheirroleinTBcontrolincludesto:
• Educate communities thateverynewborn child should receivealltheprimaryvaccinesincludingBCG
• CreateawarenessonTBtoreducestigmaanddiscrimination• Perform TB symptom screening in the community and refer
symptomaticpersonstothenearesthealthfacility• DOTsupportforpatientsonTBtreatment• IdentifyallTBpatientswhoarelosttofollowupandreferthemback
forTBtreatment• Participateinpatientsupportgroupstooffercounsellingandpsycho
socialsupport• Maintain a household register used to determine overall health
statusinthecommunity
Health facilitiesDiagnosisandtreatmentofTBisdoneinhealthfacilities,whichofferdifferentkinds of services depending on its Tier and the resources available. Thefacilitiesareclassifiedintothefollowinglevels:Level II-DispensaryLevel III-HealthcentreLevel IV- Primaryreferralunit(Sub-countyhospital)Level V-Secondaryreferralunit(Countyreferralhospital)Level VI-Tertiaryreferralunit(Nationalreferralhospital)
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Therolesofthevariouslevelsofhealthfacilitiesareasshownintable35.
Table 35: Roles of the different health facilities
Level Level 2 and 3: Dispensary and Health centre
Level 4 and 5: Sub County and County Referral Hospitals Level 6: National Referral Hospitals
Role Lowerlevelofhealthservicedelivery
ReferralfacilitiesforpatientsfromtheDispensary/Healthcentrelevels
Thisisthehighestlevelofreferralforspecializedcare
Diagnosis
-Historyofpresentingillness-PhysicalExamination-Investigations• GeneXpertistherecommended
testthereforereferspecimentoageneXpertsite
• WherereferralisnotpossibleSputummicroscopycanbedone
• FordiagnosisofEPTB,childrenshouldbereferredtoahigherlevel
• -Historyofpresentingillness• -PhysicalExamination• -Investigations• GeneXpertisdone,whereitis
notavailablereferspecimentoageneXpertsite
• WherereferralisnotpossibleSputummicroscopycanbedone
• DiagnosisofEPTBthroughX-ray,Mantoux,FNAandanyotherrecommendedtests
• Nasalpharyngealaspirationisdone
-Historyofpresentingillness-PhysicalExamination-Investigations• GeneXpertisdone• DiagnosisofEPTBthroughX-ray,
Mantoux,FNAandanyotherrecommendedtests
• Nasalpharyngealaspirationisdone
Treatment
• ChildrendiagnosedwithTBareinitiatedontreatmentaccordingtotheregimenanddosagerecommendations
• Documentation:recording,reportingandnotificationofcases
• Followupofchildrenontreatment
• Pharmacovigilance
• ChildrendiagnosedwithTBareinitiatedontreatmentaccordingtotheregimenanddosagerecommendations
• Documentation:recording,reportingandnotificationofcases
• Followupofchildrenontreatment
• Pharmacovigilance• Managementofcomplicated
caseswhorequireadmissionorindividualizedregimene.g.DRTB
• Decentralizationofdiagnosedcasestootherfacilities
• ChildrendiagnosedwithTBareinitiatedontreatmentaccordingtotheregimenanddosagerecommendations
• Documentation:recording,reportingandnotificationofcases
• Followupofchildrenontreatment
• Pharmacovigilance• Specializedpatientmanagement
forcomplicatedcasesorprovisionofindividualizedregimene.g.DRTB.
• Decentralizationofdiagnosedcasestootherfacilities
Prevention
• Healtheducation• Triaging• IPCPlans• IPT
• Healtheducation• Triaging• IPCPlans• IPT• Isolationfacilitiesforcaseswho
requireadmission
• Healtheducation• Triaging• IPCPlans• IPT• Isolationfacilitiesforcaseswho
requireadmission
Support
• Linkingpatientstootherservices
• Identificationofcontacts
• Linkagewithcommunity
• Ensuringadequacyofresourcesforpatientse.g.medicines,Humanresource
• Referralofcomplicatedcasestoahigherlevel
• Linkingpatientstootherservices
• Identificationofcontacts
• Linkagewithcommunity
• Ensuringadequacyofre-sourcesfortheSubCounty/Countye.g.medicines,Humanresource
• Linkingpatientstootherservices
• Identificationofcontacts
• Linkagewithcommunity
• Ensuringadequacyofre-sourcesfortheSubCounty/Countye.g.medicines,Humanresource
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CHAPTER 10
Monitoring and Evaluation for childhood TB
Tuberculosis is a Notifiable Disease under the Laws of Kenya (Public Health Act CAP 242: PART III)
TB treatment in Kenya is free
A notifiable diseaseisanydiseasethatisrequiredbylawtobereportedtogovernmentauthorities.Thisfacilitatesclosemonitoringofthediseaseandtimelyactiontocontrolit.
10.1 Monitoring
Monitoringistheroutinetrackingofkeyelementsofprogramperformancethroughcarefulrecordkeepingandregularreporting.Monitoringisusedtoassesswhetheractivitiesarecarriedoutasplanned.Itfocusesontheactivitiesimplemented and results achieved. It provides continuous information ontheprogressbeingmadetoachievegoalsandalertsstaffandmanagerstoproblems,providinganopportunityforthesetoberesolvedearly.Effectivemonitoringreliesonaccuraterecordsbeingmaintainedforallchildren.
RecordingThisisthepracticeofcapturingdataonpatients’managementovertimeandacrossclinicalsites.Thiswillhelptrackpatientprogressandidentifyissueswithtreatmentearlyfornecessaryinterventions.AllchildrendiagnosedwithTBshouldthenberecordedintheTBregister.Afterrecordingthechild’sinformation,thecasesshouldthenbenotifiedtotheMinistryofHealth.ThisinformationwillbeusefultotheTBprograminensuringsuccessfulplanningandimplementationofPaediatricTBactivities.
ReportingThis is the aggregation and relay of the recorded information to the nextmanagement level. This should be donemonthly, quarterly and annually.Reports should be accurate, regular and timely. This enables countrywidemonitoringofTBactivitiesandevidence-baseddecisionmaking.
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Importance of Recording and ReportingRecordingandreportingareimportantfor:
• Monitoringandevaluationofimplementationofactivitiesatdifferentlevels
• Monitorchildren’sresponsetotreatment(clinicalandphysical)• Assessprogramperformance• Programplanning• Aidingstafftoprovideadequateservicestotheindividualchild• Ensuringpatientqualityandcontinuumofcare• Sharing of information with patient and transfer of information
betweenhealthfacilities• Accountabilityforadministeredmedicines
Clinicalmonitoring,doneateveryvisit,willincludeassessingandrecordingthefollowing:
• Weight;Weighthechildmonthlyandadjustingdosageappropriately.• MonitorHeight/length;WeightforHeight/z-scoreandMUAC• Response to treatment. If there ispoor response toTB treatment,
re-evaluatethechildforpossibledrugresistanceandruleoutotherdifferentialdiagnoses
• Dosagesandregimenusedfollowtherecommendeddosagesaspertheweightbands
• Drugadherenceanddrugtoxicityorsideeffects
10.2 Evaluation
Evaluation is an episodic, in-depth analysis of program performance. Itassessesprogresstowardsoperationaltargetsandepidemiologicalobjectives.Evaluationisdonetoquantifytheimpactoftheinterventionsthathavebeenimplemented.Regularevaluation isnecessary forefficientmanagementofthepaediatricTB.Evaluationgivesthehealthcareworkeranopportunitytousethedatafordecisionmakingtoimprovequalityofcare.
In TB management, this is done periodically every 3 months for casenotificationand12monthsafterthetreatmentcompletion.Itmeasures:
• NumberofchildrennotifiedwithTB(Casefindingreports)• Treatment outcomes for the children e.g. cured, failure,
Treatmentcompletedetc.• Nutritional status- (Proportion of children with Z-scores/BMIs
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andthoseunderNutritionalSupport)• TB-HIVco-infectionrateamongthechildren• NumberofhealthcareworkerstrainedonPaediatricTB• ThequantitiesofpaediatricTBmedicinesused
10.3 Quality records and reports
TB patient management data informs the kind of interventions a patientreceives.Itisalsousefulinmakingevidence-baseddecisions.Therefore,alleffortsshouldbemadetoensurethedataandreportsgeneratedfromitareofgoodquality.
Dimensions of Data QualityDataqualitycomprisesofvariousdimensionsasshownintable36.
Table 36: Dimensions of data quality
Dimension of Data Quality Definition Consequences of Poor Quality Data
Accuracy Data measures what they are intended tomeasure
• Misrepresentationofthehealthsituationinthecountry
• Conclusive decisions cannot be drawnleadingtoProgramfailure
• Patient mis-management leading to DR-TBdevelopmentandcomplications
• Inaccurate resource allocation e.g.financial, human resource, medicines,infrastructure
• Medico-legalimplications
ValidityThe extent to which a measurement is well-foundedandcorrespondsaccuratelytotherealworld
Consistency Repeatabilityandreplicability
CompletenessData that has sufficient details i.e. aninformationsystemrepresentsthecompletelistofmeasurableindicators
Timeliness Dataisavailablewithinthestipulatedperiod
Integrity Nodeliberatebiasormanipulationofdata forpoliticalorpersonalreasons
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10.4 Recording and reporting tools
ToolsthatareusedforrecordingandreportinginformationonTBmanagementofpatientsareshownintable37.
Table 37: TB Recording and reporting tools
Facility level tools Summary registers and Forms Monthly and quarterly Reports
Sputum/XpertMTB/RIFrequestform
Tuberculosis(TB-4)FacilityRegister
QuarterlyreportonTBcasefinding
PatientRecordCard(TB&HIV) MOH711A,MOH731 AFBworkloadreport
PatientAppointmentCard(TB&HIV) OtherHIVdatasummaryforms Cohortreport
TreatmentUnitRegister(TB&HIV) IPTregister EQAreport
CultureandDSTrequestform DR-TBRegister MOH711A,MOH731
AFBregister
IPTappointmentcard
Supportsupervisiontool
TBPresumptiveRegister
ICF/IPTCards-Paeds
DR-TBPatientLogBook
DR-TBPatientAppointmentCard
CommunityMonthlyReportingTool
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CHAPTER 11
Child nutrition and TB
Malnutrition is an important public health issue particularly for childrenunder five years of age who have a significantly higher risk of mortalityandmorbidity than well-nourished children. In Kenya, the infant and theunder-fivemortalityratesare77and115per1000 livebirthsrespectively.Thenationalfigureforacutemalnutritionofchildrenunderfiveyearsoldisestimatedat6%.
Malnutrition is defined as “a statewhen the body does not have enoughof the required nutrients (under-nutrition) nor does it have excess of therequirednutrients(over-nutrition).Therearetwocategoriesofmalnutrition:AcuteMalnutritionandChronicMalnutrition.
Childrencanhaveacombinationofbothacuteandchronic.Acutemalnutritionis categorized intoModerateAcuteMalnutrition (MAM)andSevereAcuteMalnutrition(SAM),determinedbythepatient’sdegreeofwasting.Allcasesofbi-lateraloedemaarecategorizedasSAM.
Chronic malnutrition is determined by a patient’s degree of stunting, i.e.when a child has not reachedhis or her expectedheight for a given age.Totreatapatientwithchronicmalnutritionrequiresalong-termfocusthatconsiders household food insecurity in the long run; home care practices(feedingandhygienepractices);andissuesrelatedtopublichealth.
SAM is further classified into two categories:Marasmus and Kwashiorkor.Patients may present with a combination of SAM known as Marasmic-Kwashiorkor.PatientsdiagnosedwithMarasmic-Kwashiorkorareextremelymalnourishedandatagreatriskofdeath.
Admissioncriteriaforacutemalnutritionaredeterminedbyachild’sweightandheight,bycalculatingweight-for-heightas“z-score” (usingWHOChildGrowthStandard,2006),andpresenceofoedema.Allpatientswithbi-lateraloedemaareconsideredtohavesevereacutemalnutrition.Seetable38foranthropometriccriteria.
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One of the key indicators for clinicalmonitoring in children being treatedforTBisimprovementinnutritionstatus.ThereareseveralwaystomonitorthenutritionstatusofundergoingTBtreatment.Allchildrenshouldhaveabaselineweight,heightandMUAC.TheMUACwillbeanindicatorofacutemalnutrition and if recent will call for the appropriate interventions. Theweight is then assessed at every visit and appropriate drug adjustmentsmadeincaseofweightgain.
Forchildren0-59monthsofagetheirage,weightandheight/lengthistakenand Z–Scores documented as per the reference charts. For children 5-19yearstheirage,weightandheightareusedtoassesstheBMIforage.
11.1 Nutritional Assessment, Counseling and Support (NACS) process
All children diagnosed with TB should receive a nutritional assessment,counselling, and support, tailored to the individual needs of the patients,including:• Nutritionassessmentanddiagnosis Anthropometric Biochemicalinvestigations PhysicalandclinicalexaminationDietary (24 hr recall for food type/frequency and household food
security) Environmentalandpsychosocial Functional(abilitytocareforself,bedridden,etc.)
• Counseling&educationBenefitsofmaintaininggoodnutritionalstatustoaTBpatientOninfantandchildnutrition(ICN)Identifying locally available foods they can access given their own
context,foodsafetyandfoodpreparationHelpingtheclienttoplanmealsandsnackswithavarietyoffoods
tomeettheirenergy,highproteinandnutrientneedsandtreatmentplans
Identifying any constraints the client may face and find ways tominimizethem
Helpingtheclienttounderstandthepotentialsideeffectsandfoodinteractions of themedicines they are taking, and help the client
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identifywaystomanagethesesideeffectsExploringwiththeclientthecause(s)ofpoorappetiteandappropriate
responses (typeof food,disease,pain,depression,anxiety,orsideeffectsofmedications)
Counselingonhighlevelsofsanitationandfoodhygiene
• SupportNutritioncareplanTherapeutic and supplementary foods (food by prescription,therapeuticfeeds,fortifiedblendedflour)Complementaryfoodsforchildren≥6monthsMicronutrientsupplementsPoint-of-usewaterpurificationtopreventwater-bornediseaseFoodsecurityandlinkagetocommunity
Uponassessment,anthropometriccriteriaareusedtoclassifythenutritionstatusofthechildasshownintable38.
Table 38: Anthropometric criteria to identify severe, moderate and at risk categories of acute malnutrition for children and adolescents*
Indicator Severe AcuteMalnutrition (SAM)
Moderate AcuteMalnutrition (MAM)
At Risk of AcuteMalnutrition
Infantslessthan6months
W/L W/L<-3Z-Score Staticweightorlosingweightathome
StaticweightorlosingweightathomeZ-Score
Oedema OedemaPresent OedemaAbsent OedemaAbsent
Othersigns Tooweaktosuckleorfeed Poorfeeding Poorfeeding
Children6monthsto10years
W/HZ-Scores <-3Z-Score Between-3to<-2ZScore Between-2to<-1Z-Score
MUAC(6-59monthsonly) <11.5cm 11.5to12.4cm 12.5-13.4cm
Oedema OedemaPresent OedemaAbsent OedemaAbsent
Adolescent(10yearsto18years)
MUAC <16cm N/A N/A
Oedema OedemaPresent OedemaAbsent OedemaAbsent
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*AnthropometriccriteriabasedonWHOChildGrowthStandards(2006)Mid-UpperArmCircumference(MUAC) isoftenthescreeningtoolusedtodeterminemalnutritionforchildreninthecommunityunderfiveyearsold.AverylowMUAC(<11.5cmforchildrenunderfiveyears)isconsideredahighmortality riskand is criteria for admissionwith severeacutemalnutrition.Table39outlinesforMUACcriteriaforchildrenunder-fiveyears.
Table 39: MUAC criteria to identify malnutrition of children less than 5 years in the community
Severely Malnourished Moderately Malnourished At Risk of malnutrition
Lessthan11.5cm 11.5cmto12.4cm 12.5cmto13.4cm
11.2 Classifying nutrition status using weight for age
Inselectedsituationsonemaynotbeabletogetanaccurateheight.Thismayhappenin:
• Childrenwhoare-verysick,disabled,haveneurologicabnormalities,veryirritable
• Instanceswheretheinstrumentstomeasureheightarenotavailable
Insuchcircumstancesonemayuseweightforageassessmentinchildrenupto14years.UsetheweightforageWHOchartstoassessthenutritionstatusofthechild.
Todeterminethenutritioninterventiontobegiventothechild,thetriagecriteriaisasshownintable40.
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Table 40: Triage to determine treatment of malnutrition
ASK: 1.Hastherebeenanyweightlossinpreviousmonth?2.Doesthepatienthaveanappetite?3.Doesthepatienthaveanymedicalconditionthatwillimpairnutritionalstatus?4.Isthebreast-feedingchildsucklingwell?
LOOK AND FEEL FOR: Visiblesignsofwasting
CHECK:MUACWeightHeight/lengthBilateral-oedema
DETERMINE: LevelofmalnutritionusingW/Hreferencecharts(orW/A)
LOOK AT SHAPE OF GROWTH CURVE: 1.Hasthechildlostweight?2.Isthegrowthcurveflattening?
11.3 Nutrition care process
Oncenutritionassessmenthasbeendoneandadiagnosismade,thechildthenneedstohave interventionstoaddresstheirspecificnutritionneeds.Theseinterventionsincludenutritioncounselling,foodsupplementationandfoodbyprescriptionassummarizedintable41.
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Table 41: Steps in the nutrition care process
Nutrition care process
Classification of under nutrition
Severe Moderate / mild
NutritionAssessment
1.Lookforsignsofseverewasting-lossofmusclemass-severevisiblewasting2.Checkforpresenceofbilateralpittingedema–anygrade3.MeasuretheMUAC4.Takeweight5.Checkformedicalcomplications6.Conductappetitetest
1.Takeweight2.MeasuretheMUAC3.Assessdietaryintake4.Checkformedicalcomplications5.Assessthesocialeconomicstatus6.Checkforbilateralpittingoedema7.Checkforclinicalsignsofmalnutrition
NutritionDiagnosis -Signsofseverevisiblewasting-BilateralpittingOedema(+,++,+++)
Nutritionintervention
-Nutritionandinfantfeedingcounselling-Provide200Kcal/Kg/dayRUTF279gmsperdayofRUTFi.e.,(21sachetsperwk)-200-300gramsperdayFBFevery2weeksormonthly-Onebottle(150ml)ofSWS*permonth-Inpatientstabilizationcaretotreatunderlyingillnesses
-Nutritionandinfantfeedingcounselling-Provide200-300gramsperdayofFBF(formildmalnutrition)--Provide200Kcal/Kg/dayRUTF279gmsperdayofRUTFi.e.,(21sachetsperwkformoderatemalnutrition)-Onebottle(150ml)SWS*permonth-Routinebasictreatmente.g.VitaminA,deworming,ironfolicsupplementation.
Nutritionmonitoringandevaluation
-Checkweightweekly-Conductappetitetestweekly-Carryoutothernutritionassessments-Giveeducationandcounsellingasrequired.-Littleornoedemafor10daysandpassedappetitetest-continueonFBF
-Checkweightmonthlyandheighteverythreemonths-Carryoutnutritionassessmentmonthly-Giveeducationandcounsellingasrequired
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CHAPTER 12
Managing Anti-TB Medicines
12.1 Pharmaceutical management
Pharmaceutical management is a set of practices aimed at ensuring thetimelyavailabilityandappropriateuseof safe,effective,qualitymedicinesandrelatedproductsandservicesinanyhealth-caresetting.
The Pharmaceutical Management CycleThePharmaceuticalManagementCycleisasystematicapproachtoensurethatmedicinesatalllevelsofhealthcaredeliveryareconsistentlyavailableandappropriatelyused. Itemphasizes theconnectionsbetween fourdrugmanagement activities - selection, procurement, distribution and use asshowninfigure10.
Figure 10: The pharmaceutical management cycle
The cycle was developed by the Management Sciences for Health’ Centre for Pharmaceutical Management in collaboration with the World Health Organization’s Action Program on
Essential Drugs.
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12. 2 Quantification of anti-tuberculosis medicines
Quantificationistheprocessofestimatingthequantitiesofanti-tuberculosismedicinesneededforaspecificperiodtoensureanuninterruptedsupply.Quantification is an important step in procurement and ordering for re-supply.Goodquantificationensures theappropriateallocationof funds toenablepurchaseoftherightmedicineintherightquantityattherighttime.
The rationale for quantification of anti-tuberculosis medicines• To ensure that there are sufficient quantities to meet clients’ /
patients’needsandavoidshortages/stock-outs.• Toavoid surpluses thatmay lead toover-stocking, expiries and/or
wastageofcommodities.• To make informed procurement adjustments when faced with
budgetaryconstraints.
Quantification methodsThisguidelinefocusesattentiononthetwomostcommonlyusedmethods—consumptionandmorbidity.Themethoduseddependsonthetypeofdataavailable.Themainmethodsofquantificationinclude:
a) Consumption method Theconsumptionbasedmethoduseshistoricaldataontheactualmedicinesdispensed to patients to calculate the quantity of medicines that will beneededinthefuture.Whenusingtheconsumptionmethodforquantification,outofstockperiodsmustbeadjustedinthecalculation.
b) Morbidity methodThemorbidity-basedmethodusesdataaboutdiseasesandthefrequencyoftheiroccurrenceinthepopulation(incidenceorprevalence)orthefrequencyoftheirpresentationfortreatment.Itforecaststhequantityofdrugsneededforthetreatmentofspecificdiseases,basedonprojectionsoftheincidenceofthosediseases.12.3GoodinventorymanagementAninventorymanagementsystemisacycleofactivitiescomprisingordering,receiving,storageandissuingofanti-tuberculosismedicines.
a) OrderingThefacilityorderssuppliesmonthlyfromthedistrictstoreusingastandardorderform(FCDRR).ThedistrictorderssuppliesmonthlyfromKEMSAstoresusinganelectronicdistrictaggregationtool,whichalsoservesasareport.
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b) ReceivingThefacilityreceivessupplies;counterchecksagainstthestandardorderformanddeliverynote,andrecord’sthetransactiononastockcard.
c) StorageAnti-tuberculosis commodities should be stored in optimal conditions toensure their safety andefficacy in accordancewith theprinciplesof goodstoragepractices:
• Goodarrangement• Qualitymaintenance• Assuredsecurity• Goodinventorycontrolandstockrotation• Goodrecordkeeping
Disposalofunusablestockshouldbecarriedoutaccordingtotheguidelinesfor disposal of pharmaceuticals. Some commodities like PAS require coldstorage andmaintenance of the cold chain is important tomaintain theirefficacy.
d) Issuing Thefacilityissuessuppliestovariouspointsofuse,usinganissue/requisitionvoucher(S11/S12)andrecordstheissueonthebincard.
Types of inventory recordsVarious forms are used for requisitioning and issuingmedicines, financialaccounting,andpreparingconsumptionandstockbalancereportsasshownintable42.
Table 42: Types of inventory records
Record type Source document Information
Stockkeepingrecords Bincards,stockledgercard StockathandReceipts,lossesandadjustments
Transactionrecords Issueandreceiptvoucher–(S12,S11),KEMSAdeliverynotes,Standardorderform Orders,issuesandreceipts
Consumptionrecords DailyactivityRegister,Healthfacilitymonthlysummary,Districtaggregationtool,tally/ticksheet
ConsumptiondataStockoutdaysPatientnumbers
TB commodities are issued from a central store (KEMSA) and utilised atthe facility level. This process involves quantification and ordering by thefacilitiesfromtheircountystores.Thestoresinturnquantifytheirneedsand
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orderfromthenationalstore.Thenationalstorealsocommunicatestothecountiesonthestockstatus,orderingratesandcommodityreports.Theflowofinformationanddatabetweenthefacilities,countystoresandthenationalstoreisasshowninfigure11.
Figure 11: Flow of logistic Management Information
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Average monthly consumption: this refers to the average quantity of commodities consumed per month.
Months of stock: the quantity on hand expressed as the number of months that quantity should last calculated based on the commodity’s average monthly consumption.
Lead time: the time interval between when a new stock is ordered and when it is received and available for use.
Review period: The routine interval of time between assessments of stock levels to determine if an order should be placed. It is also known as order interval or re supply interval.
Maximum stock level: the amount of stock above which a facility should not exceed under normal circumstances
Minimum stock level: the amount of stock below which a facility should not fall under normal circumstances
LMUTB county reports
County Pharmacist/County TB coordinatorDistrict electronic aggregated summaries to be submitted to LMU by the 10th of every
month
TB TREATMENT SITESDaily activity register
Facility monthly summary by 5th of every month
MDR TB treatment sitesDaily summary to LMU by 5th of every
month
Information flowReport flow
Definitions of Key Inventory Management Terms
• Average monthly consumption:thisreferstotheaveragequantityofcommoditiesconsumedpermonth.
• Months of stock: thequantityonhandexpressedasthenumberofmonthsthatquantityshouldlastcalculatedbasedonthecommodity’saveragemonthlyconsumption.
• Lead time: thetimeintervalbetweenwhenanewstockisorderedandwhenitisreceivedandavailableforuse.
• Review period: The routine intervaloftimebetweenassessmentsofstock levelstodetermineifanordershouldbeplaced. It isalsoknownasorderintervalorresupplyinterval.
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• Maximum stock level: the amountof stock abovewhich a facilityshouldnotexceedundernormalcircumstances
• Minimum stock level: the amount of stock belowwhich a facilityshouldnotfallundernormalcircumstances
• Shelf life: the length of time a product may be stored withoutcompromisingitsusability,safety,purityorpotency
• Pipeline: theentirechainofstoragefacilitiesandtransportationlinksthroughwhichsuppliesaremovedfrommanufacturerstoclients
• Stock out: Non-availability of anyACT for 2 consecutive days in amonth.
M & E Indicators• Nationalreportingrate• ProportionofhealthfacilitieshavingatotalstockoutofTbpatient
packs
12.4 Rational use of anti-tuberculosis medicines
Definition of Rational Drug Use (RDU)The rational use of medicines requires that patients receive medicinesappropriatetotheirclinicalneeds, indosesthatmeettheirownindividualrequirements,foranadequateperiod,andatthelowestcosttothemandthecommunity(WorldHealthOrganization,1988).Thiscallsforrationaluseofmedicines in theentiremedicineusecyclewhose stepsareoutlined infigure12.
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Figure 12: The medicine use cycle
Importance of RDU• Irrational medicine use can destroy the benefits of a good
pharmaceutical management system and reduce the therapeuticusefullifeofaneffectivemedicine.
• Resourcesspentonprocurementarelostifthecorrectdrugsarenotprescribedanddispensedtothecorrectpatient.
Factors affecting rational use of medicines• Diagnosis - correct diagnosis based on parasitologically confirmed
diagnosis• Prescribing–prescribing/administeringtherecommendedmedicine
basedonthecorrectdiagnosis• Dispensing -correctdispensing(quantity,packagingandlabelling)of
theprescribedmedicine.
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• Patient compliance-patients’adherencetohealthworkerandlabelinstructions.
Minimum dispensing information a) InstructionsonhowtotakethedrugwithDOTb) Instructionsonhowlongtotakethemedicinec) ReportanysuspectedADRd) Clearlabelwithappropriatepatientandmedicineinformation
12.5 Pharmacovigilance
Definitions of key terms
Pharmacovigilance: WHO defines pharmacovigilance as the science ofcollecting, monitoring, researching, assessing and evaluating informationfromhealthcareprovidersandpatientsontheadverseeffectsofmedicines,biological products, herbals and traditional medicines, with the viewto identifying new information about hazards, and preventing harm topatients.
An ADR isaresponsetoadrugwhichisnoxiousandunintended,andwhichoccursatdosesnormallyused inhumans for theprophylaxis,diagnosisortherapyofdisease,orforthemodificationofphysiologicalfunction.
Adverse event: Anyuntowardmedicaloccurrencethatmaypresentduringtreatmentwith a pharmaceutical product but which does not necessarilyhaveacausalrelationshipwiththistreatment.Side effect: Any unintended effect of a pharmaceutical product occurringatdosesnormallyusedinhumans,whichisrelatedtothepharmacologicalpropertiesofthedrug.
Counterfeits: WHOdefinesacounterfeitpharmaceuticalproductasaproductthatisdeliberatelyandfraudulentlymislabelledwithrespecttoidentityand/orsource.
Ultimate goals of Pharmacovigilance are:• Therationalandsafeuseofmedicines• The assessment and communication of the risks and benefits of
drugsonthemarket• Educatingandinformingpatients
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Adverse experiences with medication ReportALLsuspectedadverseexperienceswithmedications,especiallythosewherethepatientoutcomeis:
• Death• Life-threatening(realriskofdying)• Hospitalization(initialorprolonged)• Disability(significant,persistentorpermanent)• Congenitalanomaly• Requiredinterventiontopreventpermanentimpairmentordamage
Report and adverse experience even if:• Youarenotcertainifthedrugcausedthereaction• Youdonothaveallthedetails
Tools and information flowReportingofADRsisdoneusing:
• Yellow form (PV 1) - form to capture all suspected adverse drugreactions
• Whitecard(PV4)-Alertcardforlifethreateningdrugreactions• Pinkform(PV6)-formforreportingpoorqualitymedicinalproducts
Thepharmacovigilancetoolsforrecordingpatientsideeffectsareplacedintheclinicians’roomswherepatientsareseen.Onceapatientreportsasideeffect,thisformisfilledinduplicate.Acopyiskept inthepatient’sfileforreference infutureandtheothercopysubmittedtopharmacyforonwardreportingtothePharmacyandpoisonsboard.FeedbacktoalllevelsofthesystemistheresponsibilityofthePharmacyandPoisonsBoard.Thiscouldtaketheformof:
• Recall–awithdrawalofaffectedproductbatchesfromthemarket• Labellingchange–inclusionofnewinformation• Reschedule–changeoftheregulatoryclasse.g.POMtoOTC• Withdrawal–removalofproductfromthemarket• Policychange–e.g.changeofuseofSPfromuncomplicatedmalaria
touseinIPTprophylaxis
Annex 1: Tuberculin Skin Test
ATuberculinskinTest(TST)orMantouxtest istheintradermal injectionofacombinationofmycobacterialantigenswhichelicitan immuneresponse
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(delayed-type hypersensitivity), represented by in duration, which can bemeasuredinmillimetres.TheTSTusingtheMantouxmethodisthestandardmethodofidentifyingpeopleinfectedwithM.tuberculosis.Multiplepuncturetestsshouldnotbeusedtodeterminewhetherapersonisinfected,asthesetestsareunreliable(becausetheamountoftuberculininjectedintradermallycannotbepreciselycontrolled).
Detailsofhowtoadminister,readandinterpretaTSTaregivenbelow,using5tuberculinunits(TU)oftuberculinPPD-S.Analternativeto5TUoftuberculinPPD-Sis2TUoftuberculinPPDRT23.
PreparationWhenpreparingtoadministertheMantouxtuberculinskintest,makesurethattheareaforadministeringthetesthasafirm,well-litsurface,andthatequipmentandsuppliesareready.
Supplies should include a vial of tuberculin, a single-dose disposabletuberculin syringe, one-quarter to one-half inch, 27-gauge needle with ashortbevel,arulerwithmillimetre(mm)measurements,2x2gauzepadsorcottonballs,alcoholswabs,apuncture-resistantsharpsdisposalcontainer,record-keepingformsforthepatientandprovider,andapen.
Toavoidreducingthepotencyofthetuberculin,storeitinsidearefrigeratorsothatitremainsbetween35and46degreesFahrenheitorbetween2and8degreesCentigrade.
Alsostoreandtransportthetuberculininthedarkasmuchaspossibleandavoidexposuretolight.
Discusswiththepatientwhytheskintest isgiven,what is involved intheprocedure,andwhenthepatientshouldreturnforthetesttoberead.Ifapatientcan’treturnwithinthe72-hourperiod,donotadministerthetest.Instead,scheduleanothertimethatallowsthepatienttocomeforboththetestandthereturnappointment.
It’salsoimportanttoencouragethepatienttoaskquestionsandtalkaboutanyanxietiesheorshemayhaveaboutthetest.Thatwayyoucanansweranyquestionsandeaseanyfearsthepatientmayhave.Afterprovidingpatienteducation,youshouldwashyourhands,usinganappropriatehand-washing
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technique,beforeadministering the testor anyotherprocedure involvingpatientcontact.
Administration
1. Locate and clean injection site 5–10cm(2–4inches) below elbow joint
Placetheforearmpalm-sideuponafirm,well-litsurface.Selectanareafreeofanybarrierstoplacingandreadingtheskintestsuchasmusclemargins,heavyhair,veins,sores,orscars.
Cleantheareawithanalcoholswabbycirclingfromthecentreofthesiteoutward.Allowthesitetodrycompletelybeforetheinjection.Becausesomeofthetuberculinsolutioncanadheretotheinsideoftheplasticsyringe,theskintestshouldbegivenassoonaspossibleafterthesyringeisfilled.
2. Prepare syringeLookattheviallabeltomakesurethevialcontainstuberculinPPD-S(5TUper0.1ml)andexpirationdate.
Whenyouopenanewvial,writethedateandyourinitialsonthelabeltoindicatewhenthevialwasopenedandwhoopenedit.Fillthesyringewith0.1mltuberculin.
3. Inject tuberculin (see Figure 3)TheMantouxtuberculinskintestisanintradermalinjection.Withtheneedlebevelagainstthepatient’sskin,insertitslowlyata5-15degreeangle.The5-15degreeangleisveryimportantbecausethislayerofskinisverythin.
For an intradermal injection, the needle bevel is advanced through theepidermis, the superficial layer of skin, approximately 3 mm so that theentirebeveliscoveredandliesjustundertheskin.Theinjectionwillproduceinadequateresultsiftheneedleangleistoodeeportooshallow.Whentheneedleisinsertedatthecorrectangleyoucanseethebeveloftheneedlejustbelowtheskinsurface.Next,releasethestretchedskinandholdthesyringeinplaceontheforearm.
Now, slowly inject the tuberculin solution. You should feel firm resistance
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asthetuberculinenterstheskin.Atense,palewhealthat’s6to10mmindiameterappearsovertheneedlebevel.Removetheneedlewithoutpressingormassagingthearea.
Discard theusedsyringe immediately in thedesignatedpuncture-resistantcontainer.
4. Check injection siteAfterinjection,aflatintradermalwhealof8–10mmdiametershouldappear.Ifnot,repeattheinjectionatasiteat least5cm(2inches)awayfromtheoriginalsite.
Incaseadropofbloodappearsatthe injectionsite, lightlyblotthebloodawaywithagauzepadorcottonball.
Donotcoverthesitewithanadhesivebandagebecausetheadhesivecouldcauseirritationandinterferewiththetest.
Immediatelyandthoroughlywashyourhands.
5. Record informationWrite the date and the time the test was administered, the name andmanufactureroftheinjectedsolution,thelotnumber,thetuberculindoseadministered, theexpirationdate, the forearmoralternativesite inwhichtheinjectionwasgiven,thesitelocationifyourepeatthetest,thenameofthepersonwhoadministeredthetest,andthereasonforgivingtheskintest.Remind the patient to return.
Explainhowtocarefortheinjectionsiteafterthetest.Tellthepatienttoavoidscratching thesite,keep thesitecleananddry,andavoidputtingcreams,lotions,oradhesivebandagesonit.Alsomentionthatgettingthesitewetwithwaterisnotharmful,butthesiteshouldnotbewipedorscrubbed.Returnthetuberculinvialtotherefrigerator,orothercoolingcontainer.
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Figure 13: Administration of the tuberculin skin test
Reading Theresultsshouldberead72hoursafteradministration.Apatientwhodoesnotreturnwithin72hourswillprobablyneedtoberescheduledforanotherTST.
Haveasmall,plastic,flexiblerulermarkedinmillimetrestomeasurethetest,apentomarktheedgesoftheinduration,andanalcoholpadtocleanoffthepenmarks.You’llneedthepatient’srecordorotherappropriateformsfordocumentingthemeasurementresults.
1. Inspect siteVisuallyinspectinjectionsiteundergoodlightandonafirmsurface.Use fingertips to find themargins of in duration, which is a hard, dense,raisedformation.Thisistheareathatismeasured.Sometimesthesitehaserythema,areddeningoftheskinthatcanalsohaveswelling.TheerythemashouldNOTbemeasured.
Markinduration.
2. Measure diameter of induration using a clear flexible rulerThediameterof the induration ismeasured across the forearm; from thethumbsideofthearmtothelittlefingersideofthearmorviceversa.
Place“0”ofrulerlineontheinside-leftedgeoftheinduration.
Read ruler line on the inside-right edge of the induration (use lowermeasurementifbetweentwogradationsonmmscale).
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3. Record diameter of indurationDonotrecordas“positive”or“negative”.Onlyrecordthemeasurementinmillimetres.Ifnoinduration,recordas0mm.
Figure 14: Reading the tuberculin skin test
InterpretationTSTinterpretationdependsontwofactors:
• Diameteroftheinduration.• Person’s risk of being infected with TB and risk of progression to
diseaseifinfected.
Mantouxispositiveifindurationis:• 10mminawell-nourished,HIVnegativechild• 5mminamalnourished,orHIVinfectedchild
AnegativeMantouxdoesnotruleoutTBinfectionordisease(especiallyintheHIVpositiveormalnourishedchild).
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Annex 2: Steps for Patient Management to prevent transmission of TB in Community and health care settings
Step Action Description
1. Screen
-Beginswithearly identificationanddetectionofpatientswithsuspectedorconfirmedTBdisease
-Achievedbyassigningastaffmemberinahealthfacilityandtrainedcommunityhealthworkerstoscreenpatientsforcoughandtakeimmediateaction
-PatientswithcoughorwhoreportbeingunderinvestigationortreatmentforTB*,shouldnotbeallowedtowaitinthelinewithotherpatients
-ThepatientsunderinvestigationandonTBtreatmentshouldbeweighedinthetreatmentroomandnotreferredtotheMCH/FP(wellbabyclinic)wheremothersandinfantarewaiting
-Likewise,patientswithcoughshouldimmediatelybereferredtoahealthfacility
-Carryoutactivecontact tracingofbacteriologically confirmedPTB includingMDRandXDRTB
-Activelytrackthoselosttofollowupandbringthembacktotreatment
2. Educate
-Educatetheabove-mentionedpersonsidentifiedthroughscreeningoncoughetiquetteandrespiratoryhygiene
-Instructthemtocovertheirnosesandmouthswhencoughingorsneezing
-Whenpossibleprovidefacemasks,handkerchiefsortissuesforcoveringtheirmouths
3. Triage
Patientsinspecialgroups(knownHIVpositive,theveryyoungandold)shouldbegivenpreferenceincare.Triagingsymptomaticpatientstothefrontofthelinefortheservicesshouldbedone.InanintegratedservicedeliverysettingknownHIVpatientsshouldbeseparatedfromsmearpositiveTBpatients.KnownHIVpositiveclientsinthecommunityshouldfrequentlybemonitoredforTBandreferredpromptly.
4.
Investigate forTBor
Refer
-TBdiagnostictestsshouldbedoneonsiteor,ifnotavailableonsite,thefacilityshouldhaveanestablished linkwithaTBdiagnosticand treatmentsite towhichsymptomaticpatientscanbereferred.
5. Treatment
-AppropriateTBtreatmentshouldbeinitiatedinaccordancewithNationalTBguidelinesat theearliesttimepossible.Directlyobserved therapy (DOT)toensureadherencetotreatment.Follow-upandmonitorpatientsinaccordancewithNationalTBguidelines.
-Conductadditionaldiagnosticprocedures toensure theappropriate treatment isgiven(bothforTBtreatments wel l as potentia l interact ions withothermedicationssuchasARVs).Documentcompletionoftreatment.
6.Discharge
Plan
-Forinpat ient and outpat ient sett ings ,coordinate a dischargeplanwiththepatient(includingapatientwhoisaHCWwithTBdisease)andtheTB-controlprogramofthelocal,districtorprovincialhealthfacilities.Ifapplicable,co-managemento f patientswithHIVorotherdiseasesshouldbecoordinated with the applicable sub-county orCountyhealth facilities.ForMDR-TB, identify trainedHCW in referral siteswhowillbeabletomanagethepatientaccordingtothenationalmulti-drug-resistantTBguidelines.
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Annex 3: Taking Anthropometric Measurements
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Annex 4: Growth monitoring charts
Forchildren0-59monthsofage,age,weightandheight/lengthistakenandZ–Scoresdocumentedasperthereferencecharts.Forchildren5-17yearsold,age,weightandheightareusedtoassesstheBMIforage.
Instructions for using the Z-score chart
Always ensure the child is less than 5 years when using these charts.
Step 1: MeasurementFirstdeterminetheageofthechildin“years”and“months”.For infants and children less than 2 years or if under 87cm,measure thelength in “cm”while lying down (supine.) Children over 2 years or above87cm,measureheight in“cm”whilestanding.Measuretheweight in“kg”andrecordinthepatientrecordcard.
Step 2: Read the chartConfirmifthechild’sagecorrespondstothechartfor0-2yearsor2-5yearsandidentifythecorrectchart.Identifythelength/heightcolumnonthechart.
a) Findwherethemeasuredlength/heightofthechildisonthechartandplaceyourfingeronthiscell.
b) Movealongtherowwhereheightwasidentifiedandidentifythecellwithweightthatisequaltoorlessthantheactualrecordedweightofthechild.
Step 3: ClassificationClassifyandreportthechild’sweightforheightZscorecorrespondingtotheidentifiedweightfromtheSDrowsatthetopofthechart.
Step 4: InterventionAll children with a Z-score of -2SD and below are eligible for Food byPrescription.
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Instructions for using the BMI for age chart
Always ensure the child is 5-17 years when using these charts.
Step 1: Measurement1. Confirmtheageandgenderofthechild.2. Takethechild’sheightin“cm”andweightin“kg”andrecord.3. Convertthechild’sheightto‘meters’.4. Calculatethechild’sBMIthus:weight(kg)/height(meters)2
Step 2: Reading the BMI for age1. Confirmthechartiscorrectforthegenderofthechild.2. OntheBMIforagechart,checkthecolumnmarked“Year.Month”
andidentifytheageofthechild.3. Alongthisrow,choosethecellthatisnearesttotheactualBMIyou
havecalculated.4. Thiscorrespondstothechild’sBMIforagescore.
Step 3: ClassificationClassifyand report the child’sBMI foragecorresponding to the identifiedBMIfromtheSDrowsatthetopofthechart.
Step 4: InterventionAllchildrenwithaBMI forageof -2SDandbelowareeligible forFoodbyPrescription.
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List of contributors
TheTBProgramacknowledgestheinputreceivedfromthefollowingofficerswhoworkedtirelesslyduringthedevelopmentofthisguideline.
DrJosephSitienei DivisionofCommunicableDisease PreventionandControl
DrJoelKangangi WorldHealthOrganization
DrEnosMasini NationalTuberculosis,LeprosyandLungDiseaseProgram
DrAgnesLangat CenterforDiseaseControlandPrevention
DrHermanWeyenga CenterforDiseaseControlandPrevention
DrKameneKimenye NationalTuberculosis,LeprosyandLungDiseaseProgram
DrRichardMuthoka NationalTuberculosis,LeprosyandLungDiseaseProgram
DrImmaculateKathure NationalTuberculosis,LeprosyandLungDiseaseProgram
DrShobhaVakil NationalAIDS&STIControlProgram
Prof.ElizabethObimbo TheUniversityofNairobi
DrDianaMarangu TheUniversityofNairobi
DrEvansAmukoye KenyaMedicalResearchInstitute
DrLorraineMugambi
-Nyaboga TuberculosisAcceleratedResponse&Care
DrMaureenSyowai InternationalCenterforAIDSCare& TreatmentPrograms
RoseWambu NationalTuberculosis,LeprosyandLungDiseaseProgram
DrTeresiahNjoroge CentreforHealthSolutions-Kenya(CHS)
WesleyTomno NationalTuberculosis,LeprosyandLungDiseaseProgram
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SammyArithi KenyaAssociationforthePreventionofTBandLungDiseases
DorothyMibei NationalTuberculosis,LeprosyandLungDiseaseProgram
DrEvelynKimani CountyGovernmentofKiambu
JohnMartinOmondi CountyGovernmentofKisii
DrKiogoraGatimbu NationalTuberculosis,LeprosyandLungDiseaseProgram
DrChristineWambugu NationalTuberculosis,LeprosyandLungDiseaseProgram
JeremiahOkari NationalTuberculosis,LeprosyandLungDiseaseProgram
DrMuthoniKaranja NationalAIDS&STIControlProgram
DrJacquieOliwa KenyaMedicalResearchInstitute-WelcomeTrust
RoseMuthee NationalTuberculosis,LeprosyandLungDiseaseProgram
DrBrendaMungai TuberculosisAcceleratedResponse&Care
DorothyNjagi TuberculosisAcceleratedResponse&Care
DrLauraAngwenyi NationalAIDS&STIControlProgram
SamuelMisoi NationalTuberculosis,LeprosyandLungDiseaseProgram
JamesSekento NationalTuberculosis,LeprosyandLungDiseaseProgram
DrElizabethOnyango NationalTuberculosis,LeprosyandLungDiseasesProgram