national guidelines on management of tuberculosis in children · national guidelines on management...

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.

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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



3–3.9 ¾ ¾

Dissolveone (1)tabletofRHZin 20 mlofsafedrinkingwater.

Oncefullydissolved,addthecom-pletelycrushedone (1) tabletofEthambutolandgive15ml (3/4) ofthissolutionmeasuredwithasyringe.

¾



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


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


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

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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


Capreomycin (Cm)Ototoxicity: hearing damage, vestibular, disturbance, Nephrotoxicity: deranged renal function test


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




• Pharmacovigilance• Managementofcomplicated

caseswhorequireadmissionorindividualizedregimene.g.DRTB

• Decentralizationofdiagnosedcasestootherfacilities




• 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




• Ensuringadequacyofre-sourcesfortheSubCounty/Countye.g.medicines,Humanresource




• 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


Adolescent(10yearsto18years)

MUAC <16cm N/A N/A


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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

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