report of the third who stakeholders meeting on

Report of the third WHO stakeholders meeting

on rhodesiense human African trypanosomiasis

Geneva, Switzerland, 10–11 April 2019

� 789240 012936

Report of the third WHO stakeholders meeting on

rhodesiense human African trypanosomiasis


Report of the third WHO stakeholders meeting on rhodesiense human African trypanosomiasis, Geneva, Switzerland, 10–11 April 2019

ISBN 978-92-4-001293-6 (electronic version) ISBN 978-92-4-001294-3 (print version)

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ReportofthethirdWHOstakeholdersmeetingonrhodesiensehumanAfricantrypanosomiasis iii

Contents

Abbreviationsandacronyms ........................................................................................................... v

1. Introduction .............................................................................................................................. 1

2. Openingremarks ...................................................................................................................... 2

3. Meetingobjectives ................................................................................................................... 3

4. TheglobalsituationofrhodesienseHAT .................................................................................. 4

5. Reviewoftheconclusionsofthepreviousmeeting ................................................................. 9

6. Countrystatusreports ............................................................................................................ 106.1 Kenya........................................................................................................................................... 10

6.2 Malawi ........................................................................................................................................ 14

6.3 UnitedRepublicofTanzania ........................................................................................................ 17

6.4 Rwanda ....................................................................................................................................... 22

6.5 Uganda ........................................................................................................................................ 24

6.6 Zambia ........................................................................................................................................ 30

6.7 Zimbabwe ................................................................................................................................... 33

7. EliminationofrhodesienseHATaspublichealthproblemin2020 ..........................................367.1 HumanAfricanTrypanosomiasisEliminationTechnicalAdvisoryGroup .................................... 36

7.2 Countrydossierforvalidation ..................................................................................................... 37

7.3 Validationprocess ....................................................................................................................... 38

7.4 Nationalindicators–countrystatus ........................................................................................... 39

7.5 NTDroadmap2030:targetsandindicators ................................................................................ 40

8. StrategiesforeliminationofrhodesienseHAT ........................................................................ 428.1 Overviewofeliminationefforts .................................................................................................. 42

8.2 Strategiesforelimination:case-finding ...................................................................................... 43

8.3 Strategiesforelimination:treatment ......................................................................................... 45

8.4 Strategiesforelimination:epidemiologicalsurveillance ............................................................ 45

8.4 Strategiesforelimination:IEC(information,education,communication) .................................. 46

8.6 Strategiesforelimination:coordination ..................................................................................... 46

iv ReportofthethirdWHOstakeholdersmeetingonrhodesiensehumanAfricantrypanosomiasis

9. ClinicalmanagementofimportedeastAfricantrypanosomiasisin SouthAfrica:lessonslearnt .................................................................................................... 47

10. ExportedcasesassurveillancetoolforrhodesienseHAT ....................................................... 49

11. ClinicaltrialfortreatmentofrhodesienseHATwithfexinidazole ........................................... 52

12.OneHealth:linkingeliminationofrhodesienseHATwithotherinitiatives ............................ 5512.1 Epidemiologicalstudiesinanimalsandtsetseflies,andnewmolecular

approachesinZambia ................................................................................................................. 55

12.2 Tsetsecontrolandthemanagementofr-HAT ............................................................................ 56

12.3 OverviewofPATTECactivitiesinEastandSouthAfrica .............................................................. 57

12.4 FAOandPATT:theprogressivecontrolpathway(PCP)forAfricananimaltrypanosomosis ....... 59

13. Conclusions ............................................................................................................................. 61

Annexes

1. Agenda .................................................................................................................................... 62

2. Listofparticipants................................................................................................................... 63

ReportofthethirdWHOstakeholdersmeetingonrhodesiensehumanAfricantrypanosomiasis v

Abbreviationsandacronyms

AAT animalAfricantrypanosomiasis

AU AfricanUnion

CIRAD CooperationInternationaleenRechercheAgronomiquepourleDéveloppement

CIRDES CentreInternationaldeRecherche-Développementsurl’ElevageenZoneSubhumide

CNS centralnervoussystem

CSF cerebrospinalfluid

DNDi DrugsforNeglectedDiseasesinitiative

DVS DirectorateofVeterinaryServices

ECCAS EconomicCommunityofCentralAfricanStates

FAO FoodandAgricultureOrganizationoftheUnitedNations

g-HAT gambiensehumanAfricantrypanosomiasis

HAT humanAfricantrypanosomiasis

HAT-e-TAG HATeliminationTechnicalAdvisoryGroup

IAEA InternationalAtomicEnergyAgency

ICIPE InternationalCentreofInsectPhysiologyandEcology

IEC information,educationandcommunication

MAAIF MinistryofAgriculture,AnimalIndustryandFisheries

NTD neglectedtropicaldisease

OIE WorldOrganisationforAnimalHealth

PAAT ProgrammeAgainstAfricanTrypanosomiasis

PATTEC PanAfricanTsetseandTrypanosomiasisEradicationCampaign

PCP progressivecontrolpathway

PCR polymerasechainreaction

r-HAT rhodesiensehumanAfricantrypanosomiasis

RDT rapiddiagnostictest

UTCC UgandaTrypanosomiasisControlCouncil

VBDCU VectorBorneDiseaseControlUnit

WHO WorldHealthOrganization

ReportofthethirdWHOstakeholdersmeetingonrhodesiensehumanAfricantrypanosomiasis 1

1. Introduction

2020istheyearsetintheroadmap1onneglectedtropicaldiseases(NTDs),publishedbytheWorldHealthOrganization(WHO)in2012,asthetargetforeliminationofhumanAfricantrypanosomiasis(HAT)asapublichealthproblem.IntheLondonDeclarationonNTDs,2pharmaceuticalcompanies,donors,endemiccountriesandnongovernmentalorganizationsalsocommittedthemselvestomeetingthisgoal.Jointworksince2000resultedin2018infewerthan1000casesreportedglobally,ahistoricallylownumber.ImportantmilestonesarebeingreachedinachievingthegoalofeliminatingHATasapublichealthproblemby2020.

Elimination efforts have focused on gambiense HAT (g-HAT), which is responsible for most (about 98%)reportedcases.RhodesienseHAT(r-HAT)ischronicallyneglected.Thelownumberofreportedcasesfailstoattracttheinterestofdonorsandr-HATisthusoflowpriorityforhealthdecision-makers,despiteitsepidemicpotential.Domesticandwildanimal reservoirsmakethecontrolof r-HATmorecomplex.TheOneHealthapproach involving numerous sectors beyond human health, such as veterinary services, vector control,tourismandmanagementservicesofprotectedareas,isthewayforwardtoreachthesetgoals.

The first WHO stakeholders meeting on r-HAT elimination (Geneva, 20–22 October 2014)3 boosted the multisectoral coordinationmechanismbetweenWHOandpartners to eliminate r-HAT as a public healthproblem.Contributingpartnersincludedmembersofacademia,public–privatepartnerships,nongovernmentaland international organizations, donors and national sleeping sickness control programmes. The secondstakeholdersmeeting(Geneva,26–28April2017)4reviewedprogressandidentifiedessentialactivitiesforthefuturesuchassustainedsurveillance,multisectoralcoordinationandpartnerships,innovativemethodsandtoolsforcontrol,andimprovingcapacity-building.

ThisthirdstakeholdersmeetingtookplaceasthefirstroadmaponNTDs(2015–2020)wasalmostconcludedandthe new roadmap on NTDs (2021–2030)wasbeingprepared.Itwasthetimetosharetheachievements,challengesandviewsonthegoalofeliminationamongparticipatingcountriesandimplementingpartners,andtoadvancetheprocessofvalidationofeliminationandstrengtheningofsurveillancesystemsinordertodetectanyre-emergenceofthediseasebeforereachingepidemiclevelsagain.

1 Acceleratingworktoovercometheglobalimpactofneglectedtropicaldiseases:aroadmapforimplementation.Geneva:WorldHealthOrganization;2012(WHO/HTM/NTD/2012.1.http://www.who.int/neglected_diseases/NTD_RoadMap_2012_Fullversion.pdf).

2 TheLondondeclarationonneglectedtropicaldiseases.UnitingtoCombatNTDs;2012(http://unitingtocombatntds.org/resource/london-declaration).

3 ReportofthefirstWHOstakeholdersmeetingonrhodesiensehumanAfricantrypanosomiasis.Geneva,20–22October2014.Geneva:WorldHealthOrganization;2015(WHO/HTM/NTD/IDM/2015.2http://who.int/trypanosomiasis_african/resources/9789241508650/en/).

4 ReportofthesecondWHOstakeholdersmeetingonrhodesiensehumanAfricantrypanosomiasis.Geneva,26–28April2017.Geneva:WorldHealthOrganization;2017(WHO/HTM/NTD/IDM/2017.04 https://who.int/trypanosomiasis_african/resources/WHO_HTM_NTD_IDM_2017.04/en/).

2 ReportofthethirdWHOstakeholdersmeetingonrhodesiensehumanAfricantrypanosomiasis

2. Openingremarks

DrDanielDagne,CoordinatoroftheInnovativeandIntensifiedDiseaseManagementunit,WHODepartmentofControlofNeglectedTropicalDiseases,openedthemeetingandcalleditaturningpoint,asthecurrentroadmaponNTDsisalmostconcludedandthenewRoadmap2021–2030isbeingprepared.HeintroducedDrMweleceleNtuliMalecela, thenewDirectorof theWHODepartmentofControlofNeglectedTropicalDiseases,andDrAugustinKadimaEbeja,NationalProfessionalOfficeroftheWHOCountryOfficeinKinshasa,DemocraticRepublicoftheCongo.

DrEbejawelcomedallparticipantsonbehalfofDrMagaranBagayoko,actingDirectoroftheCommunicableDiseasesCluster,andtheentireNTDteamintheWHORegionalOfficeforAfrica.Hereflectedonthepreviousmeeting and emphasized theOneHealth approach in r-HAT control.Hehighlighted that all stakeholdershavean importantroletoplay intheirareaofcompetencetofacethechallengesof thenationalcontrolprogrammes.Finally,hethankedallthepartners,whosecommitmentisgreatlyappreciatedbytheAfricanregionaloffice.

DrMalecelaemphasizedtheimportanceofthenewNTDroadmap,theproposedgoalsandmilestonesforwhichareaccessibleonline.Endemiccountries,implementingpartners,donorsandstakeholdersareinvitedtocontributeandtheirinputiscrucial.ThegoalsandmilestonesareduetobefinalizedinAugust2019.ShenotedthesignificantprogressofcountriesinwhichHATisendemictowardseliminationandthecontributionoftheDrugsforNeglectedDiseasesinitiative(DNDi)toadvancingdrugdevelopment.However,eliminationmustbevalidatedandsurveillancestrengthened.Governmentcommitmentand investmentareessentialtomaintainthatsuccess,asismultisectoralinvolvementinaOneHealthapproach.DrMalecelaclosedherremarksbyacknowledgingtheinvestmentbyallpartnersparticipatinginthismeeting.

ThemeetingwaschairedbyDrJorgeSeixas,PortugueseInstituteofHygieneandTropicalMedicine,Lisbon.ThemeetingagendaisattachedasAnnex1andthelistofparticipantsasAnnex2.


3. Meetingobjectives

Theobjectivesofthemeetingwere:

~ to sustain the commitment of national authorities and technical and financial partners to WHO’sobjectivesforr-HAT;

~ to share achievements, challenges and views on the goal of elimination as a public health problemamongcountriesandimplementingpartners;

~ todiscussstrategiesforreinforcingcontrolandsurveillanceofr-HAT;

~ to assess the status of critical technical aspects in research, development and implementation oftherapeuticanddiagnostictools,epidemiologyandvectorcontrol;and

~ toconsolidatethenetworkforcollaborationandcoordinationamongstakeholders.


4. Theglobalsituationofrhode-siense HAT

WHOhasprioritizedeliminationofHATundertheInnovativeandIntensifiedDiseaseManagementunit.Twoformsofthediseaseexist:g-HAT,theslowlyprogressingform,causedbyTrypanosoma brucei gambiense, foundinwesternandcentralAfrica;andr-HAT,thefasterprogressingform,causedbyT. b. rhodesiense, in easternandsouthernAfrica.HAT is transmittedthroughthebiteof infectedtsetseflies (Glossinagenus).ThegoaloftheHATcontrolandsurveillanceprogrammeistoeliminateHATasapublichealthproblemby2020.Since2001,thiseliminationpriorityhasbeensupportedbyapublic–privatepartnershipwithSanofiandBayer.

EliminationofHAT(g-HATandr-HAT)asapublichealthproblemhasbeendefinedasfewerthan2000casesreportedperyearatacontinentallevel,anda90%reductionofthetotalareaatriskreportingmorethanonecaseper10000peopleannually (from2004baseline levels).Forg-HAT, thenextgoal is to interrupttransmission (i.e.achievesustainableeliminationof zero reportedcases)by2030.For r-HAT, thegoal for2030istomaintaineliminationasapublichealthproblem(i.e.noareaatriskreportingmorethanonecaseper10000peopleannually).Thepursuitofthegoal forr-HAT issignificantlymorecomplexthanthatforg-HATbecauseofthepredominanceofanimalreservoirs.Thelatest(2013)technicalreportofaWHOExpertCommitteeoncontrolandsurveillanceofHAT5statesthatcompleteeliminationisnotatechnicallyfeasiblegoalforr-HATwiththecurrentmeans,butitdoesnotruleoutitseliminationasapublichealthproblem.

Itispossibletoeliminater-HATasapublichealthproblem.Itsoccurrenceisrare,andthecurrentlandscapesuggests thatsomeareasmaybewithin rangeof thisgoal.The incidenceof thedisease iswellmapped,particularlythroughtheAtlasofHAT,6whichisanessentialresourceformonitoringprogressbutwhichmaypresentanincompletepictureduetounderreporting.

Eliminationasapublichealthproblemisarelevantgoalas ithelpstoraiseawarenessofthediseaseandencouragescountriestoinvestinitscontrol.SeveralkeyelementsoftheWHOcontrolprogrammerevolvearound:(i)providingsupportandtechnicalguidancetocountriesendemicforthediseasenationallytoensureaccesstodiagnostictoolsandtreatmentforallpeopleatrisk; (ii)strengtheningsurveillancebygatheringand analysing all the data considered relevant to plan andmonitor interventions; and (iii) coordinatingstakeholdersinvolvedinr-HATelimination.Importantly,reducingthenumberofcasesisnotanend-pointinitselfbutratherthefirststeptowardsanintegrated,sustainablesurveillanceprogramme.Forthisreason,themethodofassessingthisfirststepofeliminationwillbestraightforward.Conversely,theprocesswillbemuchmorecomplexandstringentforassessingtheinterruptionoftransmissionofthedisease.

Sincethereported32850HATcasesin2000,thenumberofcaseshasdecreasedsignificantlyto<2000casesannuallyforthefirsttime:1446caseswerereportedin2017(Figure 4.1).Mostcases(77%)werediagnosedintheDemocraticRepublicoftheCongo. InGuinea,thenumberofcasespeakedat>100 in2016–2017,possiblyduetotheresumptionofcontrolactivitiesaftertheEbolacrises. Thedatafor2018arebeingfinalized

5 ControlandsurveillanceofhumanAfricantrypanosomiasis.Geneva:WorldHealthOrganization;2013(WHOTechnicalReportSeries,No.984(http://apps.who.int/iris/bitstream/10665/95732/1/9789241209847_eng.pdf).

6 SimarroPP,CecchiG,PaoneM,FrancoJR,DiarraA,RuizJAetal.TheAtlasofhumanAfricantrypanosomiasis:acontributiontoglobalmappingofneglectedtropicaldiseases.IntJHealthGeogr.2010;9:57(http://www.ij-healthgeographics.com/content/9/1/57).


butalreadyshowadecreaseto<1000casesglobally.Nationalcontrolprogrammesarethuswellplacedtoreachtheeliminationgoalsby2020.Whiletheproportionalcontributionofr-HAT(2%ofcases)totheglobalnumberofHATcasesislowcomparedwiththatofg-HAT(98%ofcases),itmustnotbeoverlooked.

Figure 4.1. NumbersofHAT(g-HATandr-HAT)casesreportedannuallysince2000,withthebenchmark(2020)forelimination(expectedcases)

r-HATisendemicinUganda,theUnitedRepublicofTanzania,Malawi,Mozambique,Kenya,Rwanda,ZambiaandZimbabwe.Since2000,therehasbeenacleardecliningtrendinthenumberofreportedr-HATcases:31in2017(fromfiveendemiccountries)and24in2018(fromthreeendemiccountries)(Figure 4.2, Table 4.1).

Figure 4.2. Numbersofr-HATcasesreportedannuallysince2001atgloballevel


Table 4.1. Numbersofr-HATcasesreportedbyendemiccountries,2000–2018

2000

2001

2002

2003

2004

2005

2006

2007

2008

2009

2010

2011

2012

2013

2014

2015

2016

2017

2018

Botswana - - - - - - - - - - - - - - - - - - -Burundi - - - - - - - - - - - - - - - - - - -Ethiopia - - - - - - - - - - - - - - - - - - -Kenya 15 10 11 0 0 0 1 0 0 1 0 0 2 0 0 0 0 0 0Malawi 35 38 43 70 48 41 58 50 49 39 29 23 18 35 32 30 35 11 15Mozambique - - 1 - 1 - - - - - - - - - - - - - -Namibia - - - - - - - - - - - - - - - - - - -Rwanda - - - - - - - - - - - - - - - - 0 0 0Swaziland - - - - - - - - - - - - - - - - - - -Uganda(Tbr) 300 426 327 338 335 473 261 119 138 129 112 84 71 43 70 28 10 13 4United Republicof Tanzania 350 277 229 113 159 185 127 126 59 14 5 1 4 1 1 2 4* 3 0

Zambia 9 4 5 15 9 7 6 10 13 4 8 3 6 6 12 8 4 3 5Zimbabwe - - - - - 3 - - 0 3 2 4 9 1 3 3 1 1 0Total reported 709 755 616 536 552 709 453 305 259 190 156 115 110 86 118 71 54 31 24

From2001to2017,Ugandareportedmorethanhalf(58%)ofthe5134r-HATcasesglobally.From2013to2017,twocountries(UgandaandMalawi)reportedthemajorityofcases(46%and39%)andthreecountries(theUnitedRepublicofTanzania,ZambiaandZimbabwe)theremainder(Table 4.1, Figure 4.3).

Figure 4.3. Distributionofr-HATcasesinendemiccountries,2013–2017(includingexportedcases)


Theoverallpopulationatrisk(i.e.thetotalnumberofpeoplelivinginareasreporting>1caseper10000peopleannually)isconstantlydecreasing,butthereremain4.2millionpeopleforwhomthediseaseremainsapublichealthproblem.Currently, therearenopopulationsathighorveryhigh riskof r-HAT,but someremainatmoderaterisk(Figure 4.4).

Figure 4.4. Populationatriskofr-HATsince2000andprogressionbyfive-yearperiods

While the coverage of the population at risk of infection has improved, a significant proportion still hasdifficultyaccessingdiagnosisandtreatmentforr-HAT.In2017,some124fixedhealthfacilitiesprovidedanydiagnosisofr-HATand44fixedhealthfacilitiesprovidedtreatmentforr-HAT(Table 4.2).

Table 4.2. Healthfacilitiesprovidingr-HATdiagnosisandtreatmentin2017,byendemiccountry

CountryDiagnosis Treatment

TOTAL ΔDxC DxP DxPhTotal

Dx Δ Tx1S Tx2M Total Tx ΔKenya 25 22 16 25 0 15 15 15 14 25 0Malawi 20 6 4 20 0 4 4 4 0 20 0Rwanda 12 12 4 12 12 0 0 0 0 12 12Uganda 37 36 12 37 -1 10 10 10 3 37 -1UnitedRepublicof Tanzania 17 5 2 17 2 4 4 4 -7 17 2

Zambia 12 12 12 12 0 10 10 10 2 12 0Zimbabwe 1 1 1 1 0 1 1 1 0 1 0Total 124 94 51 124 13 44 44 44 12 124 13

DxC,clinicaldiagnosis;DxP,parasitologicaldiagnosis;DxPh,diseasestaging;Tx1S,first-stagetreatmentwithsuramin;Tx2M,second-stagetreatmentwithmelarsoprol;∆,differencefrompreviousyear

Ofthepopulationatmoderateriskofr-HAT in2017,87%lived lessthan3hours (94%lessthan5hours)awayfromahealthfacilitycapableofdiagnosingr-HATand78%livedwithin3hours(89%within5hours)ofafacilitythatprovidestreatment.Ofthepopulationatlowrisk,69%livedlessthan3hours(84%lessthan5hours)awayfromahealthfacilitycapableofdiagnosingr-HAT,and62%within3hours(76%within5hours)ofafacilitythatprovidestreatment.


One important caveat about the data on r-HAT is underreporting. The disease progresses rapidly,whichmakesitmoredifficulttodetectcasesbecausedeathcanoccurbeforepatientsreachahealthcarefacilitycompetentindiagnosisofHAT,especiallyiftheyliveinasparselypopulatedarea.

Exportedcases(i.e.casesdiagnosedoutsidethecountryofinfection)areinfectedmostlyintouristicareas(e.g.nationalparks,wildlifereserves).Indeed,veryfewcasesarereportedfromthelocalpopulationinthesesameareas.AllexportedcasesarereportedtoWHO,becauseonlyWHOenablesaccesstotreatment.WHOcanuse the reportednumberofexportedcasesasan indicatorof thepresenceof r-HAT transmission ingeographicalareas.

Therearenoappropriate serological screening tools for r-HAT,and thereforedetectionof cases reliesonclinicalsuspicionandparasitologicaldiagnosis.Itwouldlikelybedifficulttofindasponsortodevelopanewserologicalscreeningtool.Thelowawarenessofr-HATandthelackofpreparednessofhealthsystemscouldalsoleadtomisdiagnosisofthedisease.EveninepidemicsituationssuchasinUgandaduring1988–1990,mathematicalmodelsestimatedthat39%ofcaseswentundetected,and92%ofdeathswereunreported.7 Furthermore, the increased use of rapid diagnostic tests (RDTs) for malaria, replacing examination bymicroscopy,hasreducedthenumbersofincidentalr-HATdiagnosesthroughmicroscopy.Itwaspointedoutthatrotationofexperiencedlaboratorystaffalsoreducescapacitiesfordiagnosis.

HealthcareworkersshouldbesensitizedtoreferpatientsformicroscopicexaminationincaseofanegativeRDTformalaria,aswellaspatientswithpositiveRDTwhoareunresponsivetoantimalarialtreatment.

Itwasnotedthatgreatprogresshasbeenmadetowardstheeliminationgoalandinreachingthedefinedmilestones,evenwithdeficienttools.Nonetheless,underdiagnosesandareasthatarenotwellcoveredbycontrolandsurveillanceactivities,andthuswherethesituationisnotwellknown,mustbetakenintoaccount.

7 OdiitM,ColemanPG,LiuWC,McDermottJJ,FèvreEM,WelburnSCetal.Quantifyingthelevelofunder-detectionofTrypanosomabruceirhodesiensesleepingsicknesscases.TropMedIntHealth.2005;10(9):840–9.


5. Reviewoftheconclusionsofthepreviousmeeting

Box 5.1 summarizes theconclusionsof thesecondstakeholdersmeeting (Geneva,26–28April2017)andjudgestheprogressofitsrecommendations.Thestartofaclinicaltrialtoassesstheefficacyoffexinidazolefortreatmentofr-HATmarksimportantprogress,asdoesthedevelopmentoftoolstoassessandvalidatetheachievementofr-HATelimination.Onlysomecountrieshaveforgedcollaborationandcoordinationofdifferent sectors and reinforced national coordination bodies. Several recommendations have not beenaddressed,notablyonimprovingsurveillance,developingserologicalscreeningtools,tailoringtargetproductprofilesofvectorcontroltoolsandincreasingtheuseofbloodsmearmicroscopy.

Box 5.1. ConclusionsofthesecondWHOstakeholdersmeetingonr-HATelimination in2017andwhethertherecommendationwasfollowed or not followed

CONCLUSIONS MEETING 2017 ~ Itisnecessarytoimprovesurveillancebyexpandingcountrycapacityforcasedetection.

~ Thedevelopmentofbettercontroltoolsisencouraged

¾ Developmentofserologicalscreeningtoolsisneeded. ¾ Strongdemand for extending the clinical trials of fexinidazole as a

treatmentforr-HAT.

¾ Target product profiles of vector control tools tailored to differentenvironments are needed.

¾ The increased use of rapid diagnostic tests (RDTs) for malariahas reduced the use of blood smear microscopy, diminishing thepossibilityofdiagnosingr-HAT.Theuseofbloodsmearmicroscopyinr-HATendemicareasshouldbeencouraged.

~ WHOisrequestedtoprovideguidanceontherequirements,proceduresand criteria for assessing and validating the elimination of r-HAT as apublichealthproblem.

~ r-HATendemic countries express their interest in gainingownershipofandpromoting theuseof theAtlas ofHAT at national level, providingappropriatetrainingmaterialinEnglish.

~ Collaboration and coordination of different sectors including animalhealth, agriculture, conservation of natural areas, tourism and humanhealth is required. The establishment and reinforcement of nationalcoordinationbodiesisrequired


6. Countrystatusreports

6.1 Kenya

Current situation

Epidemicsofr-HATinKenyahavebeeninterspersedwithlongperiodsoflowendemicityacrossthreemainfoci:theLambweValley,westernKenyaandtheMasaiMaraNationalReserve.Theclusterofcasesdetectedintheearly2000sinwesternKenyawasdrasticallyreducedinsubsequentyearsinresponsetojointworkbythegovernmentsofKenyaandUgandainmobilizinglocalauthoritiesandactingcollaboratively.Thetwolastcasesreportedwerein2012fromtheMasaiMaraNationalReserve.Bothcases(diagnosedinBelgiumandGermany)wereinstage1ofthedisease.Afteramassiveresponsefrommultiplegroups,nomorecaseshavebeendetectedinlocalpeopleortouristssincethen.NocaseshaveoccurredintheLambweValleysince1992andinwesternKenyasince2009.Historically,reportedcasesfromwesternKenyahavebeeninlocalpeople,whereasinMasaiMarathediseasehasbeenexclusivelyreportedintourists.

Endemic foci/regions at risk of r-HAT (Figure 6.1.1) ~ Focus1:LambweValley(RumaNationalParkoccupiesone-thirdofthevalleyfloor);

~ Focus2:WesternKenya(Busia,Teso,Bungoma,MountElgondistricts);

~ Focus3:MasaiMaraarea(MasaiMaraNationalReserveis71kmfromSerengetiNationalParkintheUnitedRepublicofTanzania).


Figure 6.1.1. Theriskofr-HATinKenya,2012–2016

Healthfacilitiescapableofdiagnosingr-HATareconcentratedinwesternKenya,wherehistoricallymostcasesoccurred(Figure 6.1.2).Clinicalseminarstosensitizemedicalandlaboratorypersonnelhavebeenprovidedsince2012.IntheMasaiMaraNationalReserveanditsenvirons,personnelinsixhealthcentresweretrainedin2012(14laboratorypersonneland71othermedicalpersonnel).NocaseshavebeentreatedinKenya’spublichealth-caresystemforatleast10years,resultinginalackofexperienceofmedicalandlaboratorypersonnelinr-HAT.Furthermore,thereisashortageofdiagnosticequipment,specificallycentrifuges.


Figure 6.1.2. Locationofhealthfacilitieswithr-HATdiagnosticcapacityinKenya,2016

HAT control activities: Ministry of Health ~ ActivitiesarecoordinatedbytheVectorBorneDiseaseControlUnit(VBDCU),formerlytheDivisionofVectorBorneDiseases

~ VBDCUhasdraftedanHATeliminationstrategy

~ Controlandsurveillancearebeingstrengthenedthroughcapacity-buildinginexistinghealthcentres

~ VBDCUcoordinates governmentaldepartments responsible for animalAfrican trypanosomiasis (AAT)andvectorcontrol

~ VBDCU isconsultingwithall relevantHATstakeholders toprepare thedossier forvalidationof r-HATeliminationaspublichealthproblemby2020

~ KenyahasinauguratedanNTDEliminationCertificationCommittee


~ Health services have been devolved to County Governments (decentralization reform) since 2014,causingsomelossofstafftrainedinHAT

~ Nationalsupportandfunding:otherhealthneedsareprioritizedduetozeroreportedHATcases

Partners in HAT and funding from partners ~ The Government of Kenya provides human resources, financial and non-financial facilitation andcoordinationofHATactivities

~ WHOprovidesantitrypanosomalmedicinesandsupportssurveillanceofHAT

~ TheUnitedStatesNationalInstitutesofHealthprovidesresearchfunding

~ TheInternationalAtomicEnergyAgency(IAEA)providesresearchcapacity-buildingandfunding

~ TheUnitedStatesCentersforDiseaseControlandPreventionfundsHATresearchandintervention

~ DNDiprovidescapacity-building

~ TheSwissTropicalandPublicHealthInstituteprovidescapacity-building

~ Other sectors active in tsetse and trypanosomiasis control

~ TheKenyaTsetseandTrypanosomiasisResearchCouncil(KENTTEC)conductstsetsecontrolactivities

~ The Kenya Agricultural & Livestock Research Organization (KALRO) supports HAT diagnosis andsurveillance,rapidresponseforsuspectedcasesandoverseesthedevelopmentofnewcontroltools

~ TheKenyaWildlifeServicefocusesonRumaNationalParkandtheMasaiMaraGameReserve

~ TheInternationalCentreofInsectPhysiologyandEcology(ICIPE)conductsresearchonvectorcontroltools

~ TheDirectorateofVeterinaryServicesengagesinveterinaryservicesanddiseasecontrol

Challenges to r-HAT control ~ AccordingtoanassessmentbyVBDCU,99%ofhealthfacilitiesand98%ofhealthworkersincountiesformerlyendemicforr-HAThavenocapacitytodetectordiagnoseHAT

~ Theabsenceofthediseasecontributestolowawarenessamongcommunitiesandhealthworkers

~ Expertiseisbeingprogressivelylostthroughtransfersandnaturalattrition,withnoreplacementofstaff

~ Diagnosisiscomplicated,andthecurrentdiagnostictoolsareinadequate

Future perspectives ~ Completether-HATeliminationstrategydocumentledbyVBDCUandtheMinistryofHealthofKenya

~ Strengthendiagnostic capacity forHAT in existinghealth facilities servingnon-traditional foci (MasaiMara);providetrainingandprogrammesupportvisits

~ Continuetodeveloporadoptnewtoolsfordiagnosisandcontrol

~ Maintain vector control activities in relevant regions and enhance control of AAT (Kenya Tsetse andTrypanosomiasisResearchCouncil,DirectorateofVeterinaryServices)

~ StrengthencoordinationofcontroleffortsamongpartnersthroughtheOneHealthapproach

~ Provideequipmentfordatamanagementandusethesedatatoplanandmonitorinterventions(e.g.HATAtlas)

~ Createandmaintainr-HATawarenessamongcommunitymembers

~ AttendmeetingsofinternationalfocalpointsonHAT

~ Synergizeeffortstosubmitthedossierforvalidationofr-HATelimination


6.2 Malawi

Current situationMalawihasthreefociofr-HATtransmissioninthecentral,westernandnorth-westernregions(Figures 6.2.1–6.2.2).Thenumbersofreportedcasesfellto11in2017and15in2018(Table 6.2.1),mostofwhichwerefromtheVwazaGameReserve(Rumphifocus).Since2016,caseshavebeenreportedinNkhotakotaGameReserveagainafter7consecutiveyearswithoutcases.Itisassumedthatr-HATwasreintroducedbyimportedcattleandelephantsin2014.ThenumberofsitestreatingpatientsandthefatalityratesaregiveninTable 6.2.2.

Figure 6.2.1. Distributionofr-HATcasesinMalawi,2013–2017


Figure 6.2.2. Theriskofr-HATinMalawi,2012–2016


Table 6.2.1. Reportedcasesofr-HAT,byfocusinMalawi,2014–2018

2014 2015 2016 2017 2018Vwaza Game Reserve- 1Casesstage1 3 20 2 0 0Casesstage2 30 5 31 7 9Total detected cases 33 25 33 7 9Kasungu National Park -2Casesstage1 0 0 0 0 0Casesstage2 3 0 0 0 0Total detected cases 3 0 0 0 0Nkhotakota Game Reserve- 3Casesstage1 0 0 0 1 5Casesstage2 2 3 1Total detected cases 0 0 2 4 6Total for Malawi 36 25 35 11 15

Table 6.2.2. Numbersoftreatmentsitesandcasestreated,andfatalityratesinMalawi,2014–2018

Treatment 2014 2015 2016 2017 2018Nrofsitestreatingpatients 4 4 4 4 4Nrofcasestreated 36 25 35 11 15Deaths 7 3 2 1 2Fatalityrate(%) 19.4 12 5.7 9 13.3

Health facilities capable of diagnosing r-HATVwaza Game Reserve

~ RumphiDistrictHospital;KatowoRuralHospitalandMwazisiHealthCentre

~ MzimbaNorthDistrict;MalidadeandThunduwikeHealthCentres

KasunguNationalPark

~ KasunguDistrictHospital

Nkhotakota Game Reserve

~ NkhotakotaDistrictHospitalandStAnne’sMissionHospital

HAT control activities developed by the Ministry of Health ~ Screeningservices

~ Diagnosisandtreatment

~ Communitymobilizationandawareness

~ Promotionandfacilitationofr-HATresearchactivities

~ Resourcemobilization

~ Disseminationofprogrammeperformance

~ Coordinationwithnationalandinternationalpartners


Control activities carried out by other sectors ~ MinistryofAgricultureandveterinaryservices:treatmentofsickanimals

~ Wildlifesector:responsiblefortsetsecontrolbysettingtrapsinparksandgamereserves

~ Academicinstitutions:planandconductresearch,anddisseminateresultsforpolicychange

Multisectoral organization and coordination ~ NationalTrypanosomiasisControlCommittee,secretariatisintheMinistryofHealth

~ Ministry ofAgriculture, Irrigation andWaterDevelopment,Ministry of PublicWorks andMinistry ofNaturalResourceschairmeetingsalternatively

~ Academicinstitutionswritereports

~ Goodcollaborationwithdepartmental,inter-ministerialandotherimplementingpartnersanddonors

~ Localpartners:ministries(MinistryofAgriculture,IrrigationandWaterDevelopment,MinistryofPublicWorks, Ministry of Natural Resources); academic institutions (Lilongwe University of Agriculture &NaturalResourcesCollegeofMedicine,KamuzuCollegeofNursing.

~ Implementingpartners:DNDi and WHO

Vector control activities ~ Trapsandtargetscoveronlyafewplacesinthethreeendemicareas

~ InchargeoftheDepartmentofNationalParksandWildlifeChallenges to r-HAT control

~ Inadequatelytrainedhealthworkers

~ Low-techscreeningtools

~ CasesreemerginginNkhotakotaGameReserveafter7yearsofnocases

~ Lackofautilityvehicleatprogrammelevel

~ TheHATprogrammeisinadequatelyfunded

Future perspectives ~ TrainHAThealthworkersinthreedistricts

~ Providehigh-techscreeningtools

~ Increasecommunitymobilizationandawareness–brieftraditionalhealersonHAT

~ Ensureroutinesupportivesupervision

6.3 United Republic of Tanzania

Current situationThefirstrecordedcaseofr-HATintheUnitedRepublicofTanzaniawasin1922inMaswaDistrict,Shinyangaprovince. Largeoutbreaks in thenorth-westernpartof thecountry throughout10endemic regionshavegeneratedmorethan90%ofreportedcases.Thenumberofreportedcaseshasdecreasedsince1995,with≤5casesreportedannuallysince2009andevenzeroreportedcasesin2018(Table 6.3.1).


Figure 6.3.1. Distributionofr-HATcasesintheUnitedRepublicofTanzania,2012–2016

Foci/regions affected by r-HAT (Figures 6.3.1–6.3.2) ~ Tabora:Urambo,Kaliua

~ Katavi: Mpanda

~ Kigoma:Kibondo,Kasulu,Uvinza(Nguruka)

~ Manyara:Magugu,Tarangire

~ Mara:Mugumu,Serengeti

Allhaveprotectedareaswithnearbynationalparks.


Figure 6.3.2. Theriskofr-HATintheUnitedRepublicofTanzania,2012–2016

Table 6.3.1. Reportedcasesofr-HATbyfocusintheUnitedRepublicofTanzania,2014–2018

2014 2015 2016 2017 2018KigomaCasesstage1 1 0 1 0 0Casesstage2 0 0 1 0 0Total detected cases 0 0 2 0 0TaboraCasesstage1 0 1 2 0 0Casesstage2 0 0 1 0 0Total detected cases 0 0 3 0 0Mara, SerengetiCasesstage1 0 1 0 3 0Casesstage2 0 0 0 0 0Total detected cases 0 0 0 0 0Total for TanzaniaCasesstage1 0 0 3 0 0Casesstage2 0 0 2 0 0Total detected cases 1 2 5 3 0


Health facilities capable of diagnosing r-HAT (Figure 6.3.3) ~ Alldistrictandregionalhospitals

~ Allhealthcentres

~ Afewdispensaries(private,refugeecamps,faithbased)

Figure 6.3.3. Locationofhealthfacilitieswithr-HATdiagnosticcapacityinthe UnitedRepublicofTanzania,2016

Table 6.3.2. Numbersoftreatmentsitesandcasestreated,andfatalityratesinthe UnitedRepublicofTanzania,2014–2018

Treatment 2014 2015 2016 2017 2018Nrofsitestreatingpatients 23 23 23 23 23Nrofcasestreated 1 2 5 3 0deaths 0 0 0 0 0Fatalityrate(%) 0 0 0 0 0


HAT control activities: Ministry of HealthCoordination

~ TheepidemiologyunitoftheMinistryofHealth,CommunityDevelopment,Gender,ElderlyandChildrenhasafocalpersonforHAT

~ TheMinistryofHealth,CommunityDevelopment,Gender,ElderlyandChildrenisamemberoftheOneHealthCoordinationUnitinthePrimeMinister’soffice

Strategies

~ HATinterventionsarepartoftheNTDMasterPlan

~ NationalOneHealthStrategy,GuidelineforSurveillanceofZoonoticDiseases

~ NationalStrategyforControlofTsetseandTrypanosomiasis(draft2018)

Fundingfrompartners

~ WHO:forantitrypanosomalmedicines,capacity-buildingandonedesktop

~ FAO:fordevelopmentofadraftstrategyfortsetseandtrypanosomiasiscontrol

Multisectoral organization and coordination ~ TheOneHealthCoordinationDesk,established in thePrimeMinister’sOffice,coordinatescontrolofzoonoses,includingHAT

~ Sixzoonoticdiseasesareprioritized,amongthemHAT

~ Anationalstrategy(guide)hasbeendeveloped;eachsectoractsaccordingly

~ PartnersinHATcoordinationframework(OneHealthCoordinationDesk):MinistryofHealth,CommunityDevelopment,Gender,ElderlyandChildren,MinistryofLivestockandFisheries,TanzaniaNationalParks,NationalInstituteforMedicalResearch,UnitedStatesAgencyforInternationalDevelopment,WHO,FAOandacademia

Vector control activities ~ Generallysmallscale

~ Innationalparks:tourism(Serengeti,Ngorongoro,Tarangire,Katavi)

~ Methodsused

¾ impregnatedtargets(nationalparks)

¾ sprayingoftouristvehicles(nationalparks)

¾ treatmentofanimals,e.g.usingisometamidiumbromide(inpastoralcommunities)

¾ sprayingofanimals(inpastoralcommunities)

¾ researchontsetsefly(vectorsandvector-bornediseases)

~ Responsible institutions: Tanzania National Parks, Ngorongoro Crater Conservation Area Authority,MinistryofLivestockDevelopmentandFisheries,DepartmentofvectorsandvectorsbornediseasesintheMinistryofHealth,VectorControlTrainingCentreTanga

Challenges to r-HAT control ~ Nocoordinatorsatsubnationallevel

~ Verylimitedfinancialsupporttofacilitateactivities


~ Shortageofskilledstaff(retiredorinexperienced)

~ OveruseofRDTsdecreasestheutilityofmicroscopy,somedispensariesdonothavemicroscopes

~ Enormousassociatedsocialstigmatization

~ Longdurationofhospitalization

~ Hard-to-reachareas

Future perspectivesLaunchandoperationalizethenationaltsetseandtrypanosomiasiscontrolstrategy

~ HATsurveillanceandcontrolactivitiesplanned

¾ rain laboratory technicians and clinicians in remainingHAT foci (includingnew suspectedareas),inviteDistrictmedicalofficersandsensitizeuseofmicroscopes

¾ Advocatefundingfortsetseandtrypanosomiasiscontroltopolicydecision-makers

¾ Conductentomologicalandepidemiologicalsurveysinnewsuspectedareas(Mbeya,Singida)

¾ Initiateapublicawareness-raisingcampaign,includinginschoolsinHAT-endemicareas

~ Partnershipforimplementation

¾ StrengthencollaborationamongHATstakeholdersundertheOneHealthumbrella

¾ Identifyandappointtsetseandtrypanosomiasisfocalpersonsfromkeyplayersinministries

¾ EstablishamultisectoralAdvisoryCommitteeontsetseandtrypanosomiasis

Inthediscussion,itwasacknowledgedthatmanyvectorcontrolprogrammesusepyrethroidinsecticides.

6.4 Rwanda

Current situationAlthoughnocasesof r-HAThavebeen reported inRwandasince1998,monitoringof thedisease shouldcontinue.Historicaldatademonstratethatthediseasewasoncepresentinthepopulation,8thatthevectorisstillpresentinthecountryandthatneighbouringcountriesstillreportr-HATcases.Figure 6.4.1 shows the distributionofhealthfacilitieswithcapacitytodiagnoser-HATasof2016.

8 ClerinxJ,TaelmanH,BogaertsJ,VervoortT.Treatmentoflatestagerhodesiensetrypanosomiasisusingsuraminandeflornithine:reportofsixcases.TransRSocTropMedHyg.1998;92(4):449–50.


Figure 6.4.1. Locationofhealthfacilitieswithr-HATdiagnosticcapacitysurroundingthe AkageraNationalParkofRwanda,since2016

HAT control activities: Ministry of Health ~ NTDMasterPlan2018–2024(finaldraft),includingr-HATsurveillanceactivities

~ KeypersonnelonHATandsurveillancetrainedin12healthfacilitiessurroundingtheAkageraNationalPark,incollaborationwithWHO(August2016):

¾ surveillancetools(e.g.workplan,reportingregisters)havebeendevelopedandsharedwithallsites

¾ sensitization/awarenesstothepopulationinriskareasisbeingconducted

¾ bloodsmeartechniqueisusedforlaboratorydiagnosis

¾ HAT-positiveslidesareavailableforqualitycontrolatnationalandsentinelsitelevels

~ CascadesupervisiontomonitorHATsurveillancesystemisintegratedwithotheractivities,bytheNTDProgramme,theNationalReferenceLaboratoryandWHO

~ Fundsareprovidedforessentialmaterials;communitysensitizationandactivecase-finding

Vector control activities ~ Animalhealth:MinistryofAgricultureandAnimalResourcesthroughtheRwandaAgricultureBoard

¾ 5000trapsfortsetseflycontrolhavebeeninstalledinAkageraNationalPark

¾ sensitizationoffarmersforbushclearing

¾ Veterinarysectorstaffareonsitetotreatinfectedanimals

¾ laboratoryisequippedfordiagnosisofAAT,butnomoleculartestinghasbeenconductedtodate


~ Wildlifesector:TheRwandaDevelopmentBoard,throughtheAkageraNationalPark,hasprocuredtrapsfortsetseflycontrol

~ PartnersinHATandfundingfrompartners: apartfromgovernmentalagencies,WHOisthemainpartner

Challenges to r-HAT control ~ Surveillanceactivities:quality controlofhealth centresbyhospitals andofhospitalsby theNationalReference Laboratory not yet systematically conducted. Semester Progress report meetings on HATsurveillanceactivitiesnotregularlyconductedwithin12sentinelsitesandother28surroundinghealthcentres

~ No formal framework for multisectoral coordination to conduct overall evaluation of implementedactivitiesinsurveillanceofAATandHAT

~ Financial:norecentresearchonHATandonvectorandspeciesidentificationofAAT.Operationalcostsforprogressandcoordinationmeetings,mentorship,etc.

~ Humanresources:additionalkeystafffromotherhealthcentressurroundingthe12HATsentinelsitesare not trained

Future perspectives ~ Conductmentorshipsupervisionandlaboratoryqualitycontrol

~ Enhancemonthlyreportingofactivities

~ Createamultisectoralcoordinationframeworkfortrypanosomiasiscontrol(OneHealthapproach)

~ Conductatrainingofotherkeystaffinhealthcentresinat-riskzones

~ Advocatetocreateacommunicationchannelwithneighbouringcountries

~ Advocateforresourcemobilizationforstudiesintrypanosomiasisanditsvectors

~ PrepareavalidationdossierforeliminationofHATasapublichealthproblem

Inthediscussion,itwasacknowledgedthatr-HATappearstohavebeeneliminatedinRwanda.

6.5 Uganda

Current situationThenumbersofreportedcaseshavesignificantlydecreasedinrecentyears,withonly4r-HATcasesreportedin2018(Table 6.5.1).ThemostactivefocuswashistoricallyLango,whichreported3ofthe4casesin2018andwhere Kaberamaido is currently the area of concern. The recent emergence of new reported casesinprotectedareas, albeit in lownumbers, is concerning. Evidence suggests that treatmentof cattlewithinsecticidescontributedtotherapidreductionofr-HATcasesinUganda,althoughadditionalfactorshavenotbeenfullyexplored.

Endemic foci/regions with risk of r-HAT (Figures 6.5.1–6.5.2)Thereare33r-HATendemicdistrictsinUgandainfivemajorfoci,inadditiontoprotectedareas,namely:

~ Ssesefocus/region:LakeVictoriabasin(Kalangala,Mukono,Buvuma,Buikwe,Kayunga)

~ Busogafocus/region(Jinja,Iganga,Mayuge,Luuka,Kaliro,Buyenda,Kamuli,Namutumba)

~ Bukedifocus/region(Tororo,Butaleja,Busia,Namayingo,Paliisa,Kibuku,Budaka,Kibuku)

~ Tesofocus/region(Bukedea,Ngora,Kumi,Serere,Soroti)


~ Langofocus/region(Dokolo,Kaberamaido,Alebtong,Lira,Kole,Apac,Otuke)

~ Protectedareas(QueenElizabethNationalPark,MurchisonFallsNationalPark)areisolatedfromotherfoci

Figure 6.5.1. Distributionofg-HAT(red)andr-HAT(blue)casesinUganda,2013–2017


Figure 6.5.2. Theriskofg-HAT(red)andr-HAT(blue)inUganda,2012–2016


Table 6.5.1. Reportedcasesofr-HATbyfocusinUganda,2014–2018

2014 2015 2016 2017 2018KalangalaCasesstage1 0 1 0 0 0Casesstage2 0 0 0 0 0Total detected cases 0 1 0 0 0NamutumbaCasesstage1 0 0 0 0 0Casesstage2 0 0 0 0 0Total detected cases 0 0 0 0 0IgangaCasesstage1 0 0 0 0 0Casesstage2 0 0 0 0 0Total detected cases 0 0 0 0 0KumiCasesstage1 0 0 0 0 0Casesstage2 0 0 0 0 0Total detected cases 0 0 0 0 0BukedeaCasesstage1 0 0 1 0 0Casesstage2 0 0 1 0 0Total detected cases 0 0 2 0 0AlebtongCasesstage1 0 1 2 0 0Casesstage2 0 0 1 0 0Total detected cases 0 1 3 0 0KoleCasesstage1 0 0 0 0 0Casesstage2 0 0 0 0 0Total detected cases 0 0 0 0 0DokoloCasesstage1 10 1 1 0 0Casesstage2 30 6 2 5 1Total detected cases 40 7 3 5 1KaberamaidoCasesstage1 2 6 0 2 1Casesstage2 26 12 2 6 1Total detected cases 28 18 2 8 2LiraCasesstage1 0 0 0 0 0Casesstage2 0 0 0 0 0Total detected cases 0 0 0 0 0Protected areasCasesstage1 2 1 2 0 1Casesstage2 0 0 1 0 0Total detected cases 1 1 3 0 1Total for UgandaCasesstage1 14 10 4 2 2Casesstage2 56 18 6 11 2Total detected cases 70 28 10 13 4


Health facilities capable of diagnosing r-HAT (Figure 6.5.3)The location ofHAT-competent health facilities follows the distribution of historical foci, creating awell-coveredarea:

~ NamungalweHealthCentreIII(Igangadistrict)

~ DokoloHealthCentreIV(Dokolodistrict)

~ SerereHealthCentreIV(Sereredistrict)

~ AlebtongHealthCentreIV(Alebtongdistrict)

~ BudopaHealthCentreIV(Kamulidistrict)

~ LwalaHospital(Kaberamaidodistrict)

~ NsiinzeHealthCentreIV(Namutumbadistrict)

~ BuikweHealthCentreIV(Buikwedistrict)

~ MasafuHospital(Busiadistrict)

~ KitamiroHCIV(Buvumadistrict)

~ KibukuHCIV(Kibukudistrict)

~ MayugeHCIV(Mayugedistrict)

Figure 6.5.3. Locationofhealthfacilitieswithr-HATdiagnosticcapacityinUganda,2016


Table 6.5.2. Numbersoftreatmentsitesandcasestreated,andfatalityratesinUganda,2014–2018

Treatment 2014 2015 2016 2017 2018Nrofsitestreatingpatients 10 10 10 10 10Nrofcasestreated 69 28 10 13 3deaths 1 2 0 0 0Fatalityrate(%) 1.4% 7% 0% 0% 0%

HAT control activities: Ministry of Health ~ Strategic framework:NTDs includingHATarecoveredbythenationalhealthpolicy, thehealthsectorstrategicanddevelopmentplanandtheNTDmasterplan

~ Structuralaspect:DepartmentofCommunityHealthandDivisionofVectorBorneDiseaseControl ~ National Sleeping Sickness Control Programme: national programmemanager; regional coordinationofficeanddistrictfocalpersons

~ Coordinationatcountry level:UgandaTrypanosomiasisControlCouncil (UTCC)withtheCoordinatingOfficeforControlofTrypanosomiasisinUgandaasitssecretariat

~ Partners:researchinstitutions,academiaandothergovernmentalsectors(representedatUTCC),namelyMakerere University, University of Gulu, DNDi,MAAIF (Ministry of Agriculture, Animal Industry andFisheries),UgandaWildlifeAuthorityandinternationalpartners(UniversityofEdinburgh)

Control activities carried out by other sectors ~ Animal health: spraying of cattle, screening and treatment: Coordinating Office for Control ofTrypanosomiasis inUganda/Tackling Infections to BenefitAfrica, academia (universities ofMakerere,EdinburghandGulu),theprivatesectorandMAAIF

~ Wildlifesector:selectivetrapdeployment ~ Vectorcontrol:trapsbyMAAIF ~ Others:sterileinsecttechniquebyMAAIF/IAEA/PATTEC

Challenges to r-HAT controlOperationalchallenges

~ Ministerial:aninter-ministerialbody(UTCC)existsbutthecontributionofthevariousministriesdiffers ~ Financial:fewresourcesareallocatedduetocompetingpriorities ~ Humanresources:stafftransfers,otheremploymentopportunities ~ Multisectoralcoordination:UTCCprovidesoverallcoordinationforsectorsinvolvedbutcontributionisuneven

~ Other:HATsurveillanceinprotectedareasisachallenge

Future perspectivesHATsurveillanceandcontrolactivities

~ Maintainandreinforceongoingpassivesurveillance ~ Increasecoverageofdiagnosticservicesthroughperipheralhealthfacilitieswherer-HATispresentlynotroutinelydiagnosed

~ Reorienthealthworkersinr-HAT ~ Sensitizecommunitiestoincreaseawarenessaboutr-HAT ~ Implementpartnerships:DNDi,FIND,UniversityofEdinburgh,MakerereUniversity


6.6 Zambia

Current situationZambiahasreportedcasesofr-HATsincethe1920sinthreemainfoci,typicallybufferzonesclosetogameparksandprotectedareas(Figure 6.6.1).Atotalof3caseswerereportedin2017and5casesin2018.Thereemergenceofthediseaseinvariousfociisofparticularconcern(Table 6.6.1).

Figure 6.6.1. Distributionofr-HATcasesinZambia,2013–2017

Figure 6.6.2. Theriskofr-HATinZambia,2012–2016


Table 6.6.1. Reportedcasesofr-HATbyfocusinZambia,2014–2018

2014 2015 2016 2017 2018MpikaCasesstage1 5 2 2Casesstage2 1Total detected cases 6 2 2ChamaCasesstage1 1Casesstage2Total detected cases 1MansaCasesstage1 1 1Casesstage2Total detected cases 1 1NyimbaCasesstage1 1Casesstage2Total detected cases 1LuanoCasesstage1 1Casesstage2Total detected cases 1MambweCasesstage1 1 1Casesstage2Total detected cases 1 1MbalaCasesstage1 1Casesstage2Total detected cases 1RufunsaCasesstage1 4Casesstage2Total detected cases 4UTHCasesstage1 2Casesstage2Total detected cases 2LundaziCasesstage1 1Casesstage2Total detected cases 1ZambiaCasesstage1 9 5 2 3 5Casesstage2 1Total detected cases 10 5 2 3 5


Table 6.6.2. Numbersoftreatmentsitesandcasestreated,andfatalityratesinZambia,2014–2018

Treatment 2014 2015 2016 2017 2018Nrofsitestreatingpatients 2 3 1 1 3Nrofcasestreated 10 5 2 3 3deaths 1Fatalityrate(%) 10%

HAT control activities: Ministry of HealthNationalSleepingSicknessControlProgramme:

~ UndertheCommunicablediseasesunitintheMinistryofHealth,dealingwithNTDs

~ FocalpointpersoninchargeofNTDs

~ NationalCoordinatorappointedbythePermanentSecretaryoftheMinistryofHealth

PartnersinHATcontrol:WHO

Multisectoral organization and coordination ~ Ministry ofHealth andUniversity of Zambia, School ofVeterinaryMedicine, in evaluating the LAMP(loop-mediatedisothermalamplification)testproject

~ OneHealthconcept(MinistryofHealthandSchoolofVeterinaryMedicine)

Vector control activities ~ AerialsprayingofinsecticidesinWesternregionandinsecticide-treatedtargetsinnationalparks

~ Responsible institutions:Ministry of Livestock and ZambiaWildlifeAuthority, PanAfrican Tsetse andTrypanosomiasisEradicationCampaign(PATTEC)/GovernmentofZambia.

Challenges to r-HAT control ~ Frequentchangesinfocalpointpersons

~ Drugdistributionsystem

~ Budgetaryconstraints,dependencyonWHO

~ Frequenttransferoftrainedlaboratorytechnologistsinendemicareas

~ Weakmultisectoralcoordination

~ Lackofqualitycontrol for r-HAT laboratorydiagnosis, lackof regular refreshercourses for laboratorytechnologistsandlackofmoresensitivelaboratorydiagnostictechniquessuchasWoo’smethod(onlyavailableinonehospital)

Future perspectives ~ Cross-bordercollaborationmeetingwithMalawiandZimbabwe(MinistryofHealthfocalpointpersonsandWHOcountryoffices)

~ SensitizationworkshopforDistrictMedicalOfficersfromr-HATendemicdistricts

~ DevelopmentofIEC(information,education,communication)materials

~ Refreshercourseforlaboratorytechnologists,pharmacistsandclinicians

~ Establishqualitycontrolforlaboratorydiagnosisofr-HAT


~ Annualsupervisoryvisitstohospitalsinendemicareas

~ Restockingofmelarsoprol

~ Communitysensitizationaboutr-HATthroughradiobroadcasts

6.7 Zimbabwe

Current situationr-HATislimitedtooneareaintheZambeziValley(Figures 6.7.1–6.7.2).Since2000,veryfewcaseshavebeenreported,but in2012some9caseswerereported forunknownreasons. In2017,3caseswerereportedwhereasin2018therewerenocases(Table 6.7.1).Historically,caseshavebeenassociatedwithproximitytotheZambeziRiverandwildlife,makingtheinterfacebetweenwildlifeandhumansamajorconcernforriskofr-HAT.Thisisespeciallyimportantastheareaisusedforsafarihuntinggroupsandhostsvisitorstonationalparks.Tsetsefliesarepresentinanareaof20000km2inthenorthernpartofthecountry,andstudiesoftheirdistributionshowapatternthatcloselymatchesthedistributionofcases.Generally,diagnosticcapacityremainspoor inhealth-care facilities,especially in theaffectedarea. Furthermore, there isno treatmentfacilityforr-HATinthefocusarea;casesaretreatedinZambiaorinhospitalsinthecapitalcity.MedicinesareonlydispensedinonepharmacyinHarare(whichis>200kmawayfromendemicareas).Awell-establishedtsetsecontroldivisionisinvolvedinvectorcontrolthroughvariousmethods.

Figure 6.7.1. Distributionofr-HATcasesreportedinZimbabwe,2013–2017


Figure 6.7.2. Theriskofr-HATinZimbabwe,2012–2016

Table 6.7.1. Reportedcasesofr-HATbyfocusinZimbabwe,2014–2018

2014 2015 2016 2017 2018MakutifocusCasesstage1 2 3 1 2 0Casesstage2 1 0 0 1 0Total detected cases 3 3 1 3 0

HAT control activities: Ministry of HealthNationalSleepingSicknessControlProgramme:

~ UnderthecommunicablediseasesunitintheMinistryofHealth,dealingwithNTDs

~ FocalpointpersoninchargeofNTDs

~ NationalCoordinatorappointedbythePermanentSecretaryoftheMinistryofHealth

PartnersinHATcontrol:WHO

Multisectoral organization and coordination ~ TheDirectorateofEpidemiologyandDiseaseControlhousestheNTDsunit

~ Close, sustained collaboration with veterinary services in the Ministry of Agriculture (One Health,integratedvectorcontrol)

~ PrivatephysicianandpharmacistconductingcasemanagementinHararewithsupportfromWHOforsupply(medicinesaredistributedfreeofcharge)

~ TheNationalHealthStrategy2016–2020andtheNationalNTDStrategy2012–2016addressNTDs


Control activities carried out by other sectors ~ Animalhealth:dippingof livestockusingdeltamethrin,surveillanceandcontrolofAAT inaccordancewiththeProgressiveControlPathway

~ Vectorcontrolinterventions

Vector control activitiesMethodsused:

~ TsetsesurveysusingMan-screenfly-roundsandtraps

~ Odour-baitedinsecticide-treatedtargetsandinsecticide-treatedcattle

~ Groundspraying(2012–2013)

~ Sterileinsecttechnique:entomologicalbaselinedatacollection,dronereleasefeasibilitytrial

Areas/regionscovered

~ MolaareaadjacenttoMatusadonaNationalPark,north-westZimbabwe;sterileinsecttechniqueprojectto be implemented in 1200 km2ofthenationalpark.

~ MakutiHATfocusarea(northerndistrict)

Responsibleinstitutions:DivisionofTsetseControlServices–DepartmentofVeterinaryServices(MinistryofLandsAgriculture,Water,ClimateandRuralResettlement)

Challenges to r-HAT control ~ Lowlevelofawarenessamongmanagement,professionalsandcommunitiesaboutHAT

~ HATprevention,control,managementiscurrentlynotprioritized

~ NodedicatedresourcesareavailableforHAT

~ Notrainingprogrammeandhencenocapacitytodetect,confirmandtreatHATcases

~ The supply of antitrypanosomal medicines by WHO is appreciated, but access is limited throughcentralization

~ Poorsurveillanceforearlydetectionandreportingofcases

~ Nocasemanagementguidelines

Future perspectives ~ EstablishaNationalSleepingSicknessControlProgrammewithintheNTDTaskforce

~ Mapthedistributionofallpartnerswithcapacitytocontrol,detectandmanager-HATinthecountry

~ StrengthentherapiddiseasenotificationsystemforHATsurveillance,managementandcontrolactivities

~ Developajointreportingplatformwithveterinaryservices

~ Re-mapthegeographicalareaofriskbasedonvector,parasiteandhumancasestobettertargetcontroltowardselimination.


7. EliminationofrhodesienseHATaspublichealthproblemin2020

7.1 Human African Trypanosomiasis Elimination Technical Advisory Group

TheHATeliminationTechnicalAdvisoryGroup(HAT-e-TAG)wasestablishedin2016toassistWHOindefiningthecriteriaandproceduresforthevalidationandverificationofHATelimination.Thetargetfor2020(i.e.eliminationasapublichealthproblem)mustbevalidated.Thetargetfor2030(i.e.zerotransmissionofg-HAT)mustbeverified.Forthat,thestatusofHATeliminationincountriesmustbeassessedagainstobjectivecriteriaandtheachievementformallyrecorded.HAT-e-TAGreviewstheindicatorstoassesstheachievementofHATelimination,devisestemplatesfornationaldossiersonvalidation/verificationandestablishestheprocedurestoreviewthenationaldossiers.Italsodefinestheproceduresforpost-eliminationsurveillanceandrevisesthenationalstatus.Theprocessisperiodicallyreviewed,accordingtoscientificadvancesandtools.

HAT-e-TAGcomprisessevenmembers,withoutconflictof interests,whoareappointedfor2yearsonthebasisoftheirpersonal(notinstitutional)expertise,andsixadvisorswhorepresenttheirorganizations.Theadvisorsdonotparticipateinfinaldecisions.MeetingsareheldannuallyattheinvitationofWHO.

ThefirstHAT-e-TAGmeeting(Geneva,23–25November2016)refinedthetarget/indicatorsforeliminationofHATasapublichealthproblem.Theglobaltargetwasoriginallydefinedas:<1newreportedcase/10000inhabitantsperyearinatleast90%offoci,with<2000reportedcasesperyearatcontinentallevel.Asfociarenotobjectivelymeasurable,andastheareaatriskofHATcanbebettermeasuredinastandardizedway,HAT-e-TAGrefinedthetargetfor2020as:a90%reductionoftheareaatriskreporting≥1case/10000peopleperyear.Theprimaryindicatorsarethusthenumberofcases(asbefore)andtheareaatriskreporting≥1case/10000peopleperyear.ThisnewindicatorwasendorsedbytheWHOStrategicandTechnicalAdvisoryGroup forNeglectedTropicalDiseases at its tenthmeeting (Geneva, 29–30March2017) and is now theofficialmetric.The90%reductionreferstoabaselineoftheareaatriskcalculatedoverthe2000–2004time-period.Thesecondaryindicators(asbefore)aregeographicaldistributionofHAT,levelofriskofpopulation,andcoverageofsurveillanceandcontrol.

Thenewdefinitionoftheindicatorandtargetisappropriateatthegloballevel.However,HAT-e-TAGadvisedthat this particular indicator should not be established at a national level because it requires advancedexpertiseingeographical informationsystemsandsoftware,whichnationalprogrammesoftenlack.Asanoutcome of the second HAT-e-TAGmeeting (Geneva, 26–28 April 2017), national-level indicators of HATeliminationasapublichealthproblemweredefined(seesection7.4).

Forthevalidationofg-HATelimination,atemplatefornationaldossierswasdeveloped.AfirstvalidationdossiersubmittedbyTogoandadraftdossiersubmittedbyCameroonwereusedtoassesstheappropriatenessofthetemplateandtobuildtheassessmentcriteriaduringthethirdHAT-e-TAGmeetingin2018.Thesurveillanceplanforthepost-validationphase(chapter7ofthedossier)isespeciallyimportant.Furthermore,thecountryvalidationdossier for g-HATwas adapted for r-HATandafirst versionwas submitted to thismeeting fordiscussion(seesection7.2).


7.2 Country dossier for validationThe validation dossier documents the achievement of elimination of HAT as a public health problem byprovidingtheinformationandrequirementstodemonstratetheabsenceof(orlowlevelof)transmission.Thekeyelementsofthedossieraretoassurethepresenceofafunctionalsurveillancesystemcapableofdetectingpossiblecases.Theversionofthedossieradaptedforr-HAThaseightchapters:

1. Description of the country and its capabilities

1.1 Generalinformationaboutthecountry• Geographical,demographic,economic• Tourismactivitiesinprotectedareas

1.2 Thecountry’shealthsystem• Basicdescription,structures,capabilities• Utilization,attendancerates

2. Historical data and description of endemic areas

2.1 HistoricalHATdata(essential)• Distributionoffoci,controlactivities• Casesperyear,atleastsincethe1960s

2.2 Description/demarcationofcurrentendemicareas(essential)• Howthecountrydefinesendemicareas• Grayareas(potential,butnoinformation)• Annualnumberofvisitors

3. HAT surveillance and control activities

3.1 StructureandcapabilitiestocombatHAT(essential)

3.2 Activescreeningstrategy

3.3 Passivescreeningstrategy(essential)

3.4 Responsetosuspected/confirmedcases(essential)• Concreteactionstaken

3.5 AnalysisSWOT

4. HAT epidemiological data

4.1 Currentdata,nationallevel(essential)

4.2 Dataforthepast5years,byhealthdistrict(essential)• HATcases(S1/S2),malariatesting(bloodsmear/RDT)

4.3 Datafollowingthenationalindicatorofelimination(essential)

4.4 HATinneighbouringcountries

5. Vector control

5.1 Vectorcontrolstrategy• Approach,protocols/toolsandmethodsforevaluatingresults• Time-period,spatialcoverageinrelationtothepresenceofthedisease

5.2 VectorcontrollinkedtoHAT,results


• Tsetsedistributionmaps,ifpossiblebyspecies• Tsetsedensitydata,trackedovertime• Proportionoffliesinfectedwithtrypanosomespathogenicforhumans

6. Interventions regarding animals

6.1 Data on AAT• Farmingsystems,presenceofTrypanosoma bruceiinanimals,livestockdensity

6.2 CapabilitiestocombatAAT• Actors,methods,coverage,linkswiththehealthsector

6.3 ActivitiesforOneHealth• AnimalinterventionstrategiesforHATcontrol• Linkswiththehealthsector• Partners

7. Plan of post-validation surveillance (essential)

7.1 Eliminationstatusmustbemonitored• Surveillanceandresponseactivities

7.2 Planofsurveillanceforthenext5years• Resourcesavailable,partnersinvolved

7.3 Tomaintaintheacquiredstatus

7.4 Movetowardstheeliminationofthetransmission

8. References and annexes

The dossier allows health ministries to formally submit to WHO the claim of HAT elimination and thesupportingdata.AtemplateisavailableinFrenchandEnglish.Eligiblecountriesareencouragedtoapplyforvalidationandareinvitedalsotoprovideconstructivefeedbacksoastoimprovetheprocess.

7.3 Validation processAnad-hocreviewingvalidationteamwillbeconstitutedtoevaluatethecompleteness,accuracyandreliabilityofagivencountrydossier.TheteamascertainsthelikelihoodthatHATisnolongerapublichealthproblemin thecountry, that the indicatorsestablished for thispurposearemet,and that the surveillance systemproposedisadequateandabletodetectanyre-emergenceofthediseasebeforereachingepidemiclevels.Theteamof1–2expertsisidentifiedfromapanelofexpertsselectedbytheWHORegionalOfficeforAfricaplus1–2expertsfromHATe-TAGandmembersoftheWHOsecretariat(WHORegionalOfficeforAfricaandWHODepartmentofControlofNeglectedTropicalDiseases).Followingthetemplate,eachteammemberpreparesareportthatwillbeshared.TheWHOsecretariatcoordinatestheprocessandpreparesthefinalreport,whichisagreedon.ThefinalreportisalsosubmittedtotheWHORegionalOfficeforreviewAfricaand, ifagreed,endorsedbytheRegionalDirector.Finally, theWHODirector-General formallynotifiestheMinistryofHealth inwriting,andthe information ispublished in theWeeklyEpidemiologicalRecordandtheGlobalHealthObservatory.Areassessmentisforeseenafter5years.Figure 7.3.1showsthepathwayforvalidation.


Figure 7.3.1. PathwayforvalidationofHATelimination

AFRO,WHORegionalOfficeforAfrica;HQ,headquarters;MoH,MinistryofHealth;PHP,publichealthproblem;SOP,standardoperatingprocedure

Inthediscussion,itwasproposedthattheexperiencesgainedandtheproceduresestablishedforvalidationbe published to serve as an example of good practice for other diseases to follow on the path towardselimination.

7.4 National indicators – country statusThe global targetforeliminationofHATasapublichealthproblemby2020isdefinedasfollows:

~ <2000casesreportedannuallyatcontinentallevel

~ 90%reductionofthetotalareaatriskreporting≥1case/10000peopleperyear(from2004baselinelevels)

Theglobaltargetandtheindicatorsarenotdirectlyapplicableatcountrylevel;theymustbeadaptedinasimpleandeasilymeasurablewaytothenationalcontext.

The target at country levelfortheeliminationofHATasapublichealthproblemby2020wasdefinedbyHAT-e-TAGasfollows:

~ <1case/10000peopleinallhealthdistrictsofthecountryduringthepreviousfive-yearperiod

A health district is the internationally accepted health administrative and operational division (healthmeasuresimplementationunit).Thisgeographicalareaincludesallcomponentsofahealthsystemrequiredtodelivercommunityhealthcare.

Tocalculatethenationalindicators,thenumeratoristhemeannumberofcasesreportedannuallyfortheprevious5yearsinadistrict.Casesarenotifiedbythenationalsleepingsicknesscontrolprogrammeinthehealthdistrictaccordingtothenationalcasedefinition.The5-yearperiodsmoothsanyvariationsofcoverageandreportingfromoneyeartoanother.


Thedenominatoristhepopulationofthehealthdistrictatthemid-yearperiod.Thesourcesforestimatingthehealthdistrictpopulationcouldvary(census,datacollectedbythenationalprogrammeorbythehealthsystem,datafromgeospatialdatasets,etc.)andthereforethesourceshouldbespecifiedinthereporting.

Theindicatoriscalculatedforeachhealthdistrict.Alldistrictsofthecountryshouldhave<1case/10000people,asanaverageoftheprevious5years.Thereisnooverallcalculationforthecountry.Thisindicatorpreservestheideaoftheglobalindicatorbutgreatlysimplifiesthecalculationofthedenominatorfornationalprogrammes.However,healthdistrictsarenothomogeneous,standardizedentities.Theindicatorcouldthusbebiasedbythepresenceofpopulationagglomerations inthedistrict.TheareaofHATtransmissioncanalsooverlapseveraldistricts.Therefore, theassessmentof thequalityof thedataprovidedandthe localcharacteristicswillbeessential.Figure 7.4.1categorizestheeligibilityofcountries inwhichr-HATisendemicaccordingtonationalindicatorsandcontrolandsurveillanceactivitiestofacilitatetherequestforvalidationofelimination.

Figure 7.4.1. Eligibilityofr-HATendemiccountriesforclaimingvalidationofelimination, byepidemiologicalsituationandstatusofsurveillanceandcontrolactivities,asof2018

Currently,onecountry(Togo)hasrequestedvalidationoftheeliminationofg-HATandthreecountries(Benin,Cameroon andGuinea) arepreparing their country dossiers. Five countries are expected tobe validatedby 2020 (including one r-HAT endemic country) and 15 countries by 2025 (including 3–4 r-HAT endemiccountries). Eligible countries are encouraged to apply for validation.

7.5 NTD roadmap 2030: targets and indicatorsIn2012,WHOestablishedthegoaltoeliminateHAT(g-HATandr-HAT)asapublichealthproblemby2020.Theglobaltargetisdefinedas:

~ <2000casesreportedannuallyatcontinentallevel

~ 90%reductionofthetotalareaatriskreporting≥1case/10000peopleperyear(from2004baselinelevels)


Beyondthat,thegoalsforeliminationofg-HATandr-HATby2030differasfollows:

~ Tointerrupttransmission(sustainableelimination)ofg-HATby2030

¾ Indicator:casesofg-HATdeclaredperyear

¾ Target:zerocasesby2030

~ Tomaintaineliminationofr-HATasapublichealthproblemby2030

¾ Indicator:areaendemicforr-HATreporting≥1case/10000peopleperyear

¾ Target:noareaendemicforr-HATreporting≥1case/10000peopleperyearby2030

Thereliabilityoftheindicatorsisstronglydependentonthecapacitytodetectcases,andunderreportingisaspecialconcernforr-HAT.

Whenmeasuringprogresstowardseliminationofr-HATasapublichealthproblem,milestonesshouldbedefined(e.g.2023,2025,2027)anddifferentindicatorsandtargetsconsidered,namely:

~ Number of r-HAT cases reported.Thisindicatorhasbeenuseduntilnow.Itisexpectedthatthenumberofcaseswilldecrease,butitisdifficulttodefineafigureasatargetandmilestones.In2030,thenumberofcasesofr-HATshouldbesporadic.

~ Areas of high or moderate risk (reporting ≥ 1 case/10 000 people per year).Theseareasareexpectedtodecreaseto0in2030andmilestonesshouldbedefined.

~ A secondary indicator is required to indicate the expected improvement inaccess to diagnosis and treatment for people at risk,namely:

¾ theat-riskpopulationlivingwithin1hour’stravelofacompetentfacility(underdiscussion)

¾ theat-riskpopulationlivingwithin5hours’travelofacompetentfacility(underdiscussion)

¾ theproportionofHATcasesreceivingappropriatetreatment(>99%)

~ Asaprocessindicator,acertainnumberofcountries should be validated progressively for elimination of HAT as a public health problem:

¾ In2021:atleastfivecountries

¾ In2025:atleast15countries(3–4r-HAT)

ThesetargetsareincludedintheframeworkofthenewNTDroadmap(2021–2030).Goal3.3oftheUnitedNationsSustainableDevelopmentGoals is,by2030,“toend theepidemicsofAIDS, tuberculosis,malariaand neglected tropical diseases [including HAT] and combat hepatitis, water-borne diseases and othercommunicablediseases”.Theglobal target forNTDs is,by2030,toreduceby90%thenumberofpeoplerequiring interventionsagainstNTDs.During2019,WHOwilladopt indicatorsandtargets for2030forallNTDsandpublishthemin2020aspartofthenewNTDroadmap.


8. Strategiesforeliminationof rhodesiense HAT

8.1 Overview of elimination effortsThelife-cycleofr-HATismostlyzoonotic,involvingbothdomesticandwildanimalsasthemainreservoirsoftheparasiteandofthevector Glossinaspp.,commonlyknownasthetsetsefly.Occasionally,humansacquiretheinfectionasaccidentalhosts,whichalthougharelativelyrareeventprovokessevereillness,deteriorationanddeathunlesscasesarediagnosedandtreatedpromptly.Asthelife-cycleofr-HATinvolvesmanyhosts,multipleinterventionsareavailabletargetingdifferentpartsoftheparasitelife-cycle(Figure 8.1.1).

Figure 8.1.1. Life-cycleofr-HATandmethodsofinterventiontargetingdifferentstagesofthedisease

Numeroussectorsareinvolvedinr-HATcontrolbeyondhumanhealth–suchasveterinaryservices,vectorcontrol,tourismandmanagementservicesofprotectedareasaswellaswildlife–allofwhichcontributetoaOneHealthapproach.Eachsectorleadsspecificactivities,whichdifferbycountry,butallsectorscanandshouldactivelycollaborateintheirrespectivefieldsinsurveillanceandIECactivities.Involvementfromlocalauthoritiesisalsoneeded.

Themethodsused to control the vector include tsetse screens and traps, the sterilized insect technique(release of sterile tsetsemales), insecticide impregnated net fencing and large-scale insecticide spraying(groundoraerial).Personalprotectionmethodssuchasuseofinsectrepellentsandminimizingskinexposurearealsopromotedforpopulationsthatmaybeatrisk.


Approachestor-HATcontrolmayvarybasedonthepresenceofwildlifereservoirsversuscattlereservoirs,forwhichdifferentmonitoringandcontrolmethodsarerequired.Activescreeningisrarelyapplicableforareasinwhichwildanimalsarethemainreservoir,butpassivescreeningcanbeeffective.Protectedareasandparksareavitalsourceofincomeforcountriesandshouldberecognizedashighprioritiesforsurveillancebypolicy-makers.IncorporatingthisOneHealthapproachisimportantecologicallyandforlocalworkers,whoareconstantlyexposed.

Forareasinwhichcattlearethemainreservoir,activeandpassivescreeningisthemethodused.TreatmentofcattleasapreventiveorcurativemeasureisseentocontributesignificantlytotheeliminationofHATand,additionally,protectscattleagainstotherinfections.Treatmentincludessprayingthelegsandbellyofcattlewithinsecticide(restrictedapplicationprotocol).

InterventionsonhumansisthesectorcoveredbyWHOandincludediagnosisofhumancases(case-finding)and treatment. If a surveillance system is in place,WHO can produce pertinent information on diseasedistributionthathelpstotargetinterventionsmoreeffectivelyinallsectors.DatacollectedbythecountryandsubmittedtoWHOareverifiedandenteredintotheAtlasofHAT,whichismadeavailabletocountriesandpartnersonrequest.Itwasnotedthatcountry-levelriskassessmentsshouldtakeintoconsiderationallcomponentsofepidemiologicalinformation,whichcouldhelptowardsachievingthegoalofeliminationandsustainedsurveillance.Forexample,countriesshouldensurethathealth-carefacilitiesrecordthelocationoflikelytransmission,asthisismoreinformativethanthepatient’shometown.Theyshouldalsoensurethatexportedcasesare included in thecountry reports.This isespecially importantnowthat the intensityoftransmissionisreduced.

WHO offers training on diagnostics for clinical and laboratory staff, provides equipment and materials(including treatment) to national programmes and supports the supervision of health facilities offeringHATservices (e.g. refreshingawarenessperiodically,providingadvicewhenrequested).AntitrypanosomalmedicinesaredonatedfreeofchargethankstothepartnershipestablishedwithSanofiandBayerforthepast18years.WHOisresponsibleforforecastingtheamountsneededandwheretheyneedtobeallocated,andprovidesguidanceonhowthesupplyshouldbeusedeffectivelyandbeforeexpiry.

WHOisresponsiblealsoforadvocatingcontinuedsupportfromnationalauthorities,internationalactorsandthescientificcommunity,especiallyastheincidenceofthediseasedeclinesandthushaslimitedappealandawarenesstomany.Raisingawarenessofthediseasealsoappliestoexposedpopulationsandhealth-careworkers.

Whilepromotingtheeliminationofr-HATiscertainlywithinWHO’sremit,itsscopeofactionislimitedtothehumanhealthsector.TheOrganization’sstrengthliesinitsconveningpowerandabilitytocoordinatenationalandinternationalactors,devisecommonstrategiesandplanactivities.Toeliminatethedisease,interactionbetweennationalhealthworkersandveterinaryscientistsmustbestimulated,astheywillberesponsibleforeliminatingthediseasefromtheanimalreservoir.Attheinternationallevel,WHOiscollaboratingwithrelevantorganizations,namelyFAO(theFoodandAgricultureOrganizationoftheUnitedNations),IAEAandOIE(theWorldOrganisationforAnimalHealth).Consolidatingthisinteractionwillbecrucialtoachievingtheeliminationgoal.

8.2 Strategies for elimination: case-findingThemostimportantdecisionforsuccessfulcase-findingisthechoiceofsurveillancesites.Siteselectionistheresponsibilityofthenationalprogrammecoordinator.Surveillancesitesneedtobenearareasoftransmissionandbewellattendedandsufficientlystaffed(alwaysconsiderexistingfacilitiesfirst),withlaboratoryfacilitiespresentandexperiencedstaffandaccessibility/communicationwiththecentral level.CountrieshavesentWHOanexhaustivelistofhealthfacilitiesthatconductclinicaldiagnosis,parasitologicaldiagnosisanddiseasestagingforr-HAT.Thislistwillbeupdatedregularlytotrackchanges,asitisusefulformanagementaswellasformappingthehealthcoverageofendemicareas.


Thedistributionofhealth-carefacilitieslayeredoverthedistributionofr-HATriskcaninformcountriesabouthowto improvethepositioningoffacilitiestocovera largernumberofsusceptiblepeople(Figure 8.2.1).Areaswithreported infectionsbutnohealth-carefacilitiescan indicateneglectedareas,asdistancefromhealth-carefacilities isamaincontributingfactorforhealth-seekingbehaviourfrompatients.AnextremeexamplecanbeseeninZimbabwe,wheretheonlyHAT-competentdiagnosticfacility is locatedinHarare,hundredsofkilometersawayfromtransmissionareas.

Figure 8.2.1. Positioningofsurveillancesitesrelativetoriskareas(a)Malawi,(b)Uganda, (c)UnitedRepublicofTanzania,(d)Rwanda,(e)Zambia,(f)Zimbabwe,(g)Kenya

(a) (b)

(c) (d)

(e) (f)

(g)


Otherwaysofimprovingcase-findingincludetrainingclinicalstafftobetterrecognizethesignsandsymptomsofr-HAT,withtheuseofsupporttoolssuchaspostersorinformationsheets.Achecklistoffrequentsymptomscanaidclinicalstaffindiagnosingr-HATandhelptohighlightitspresenceinendemicareas.Cascadetrainingforperipheralhealthfacilitiesisawayofbuildingcapacityandcost–effectivelyspreadingknowledgeofthediseaseoutwardsfromsentinelsites.Itisimportanttoexaminehowhealthsystemsworkineachcountry,aseachcountryhasitsownneeds.Decisionsaboutdiagnostictestingrelyontheclinician,soawarenesseffortsandguidanceshouldtargetclinicians.Improvingawarenessofr-HATamongtraditionalhealerscouldalsobebeneficialforsupportingearlyreferraltohealthfacilities.

Training laboratorystaffcanalso improvecase-finding.Forexample,each localnetworkcouldbegivenacustomizeddecision treeofavailablediagnosticmethods, ranging fromsimple tocomplex, inadditiontoposters and information sheets on r-HAT.Often, diagnostics are unavailable due to a lack of equipment,whichshouldbereviewedandreinforcedbythenationalprogrammewhereneeded.Microscopyslidesoflaboratory examinations should be saved for quality control and competency assessment, togetherwithsamples/images/videos of trypanosomes that can be used to refresh staff knowledge and be passed ontonewstaff.Regularsupervision isneededforqualitycontrolandmotivationofstaff. Itwasnotedthatasupervisor’schecklistcouldbeuseful(alreadydevelopedforg-HAT).

Active screening for r-HAT is usually reactive rather than prospective. It targets the family and village oftheinfectedpersonandshouldbedoneimmediately.Currently,activescreeningisbasedonparasitologicalscreeningofaselectedpopulation.Datacollectiononthenumberofsuspected,testedandconfirmedcasescouldhelp inmonitoring trends in the incidenceof thedisease.Aquestionnaire hasbeen introduced insomecountriestargetedatreferringdoctors,relatingtothedetailsofsuspectedcases(patienthistory,travel,activities).

8.3 Strategies for elimination: treatmentTreatmentforr-HATmustberapidandreadilyavailable.Themedicines,availablefreeofcharge,mustbeorderedintimeandthesuppliesmustbeappropriatelymanagedbythenationalprogrammes.WHOprovidesguidanceandtechnicalsupportonmanagingsupplyandhasalsomappedhealth-carefacilitieswhichprovidetreatment,basedondatasubmittedbycountries.Thisinformationisallfedbacktonationalfocalpointsandsummarydataareavailableonline.

8.4 Strategies for elimination: epidemiological surveillanceSurveillanceofr-HATstartswithcollection,validationandconsolidationofdatabythenationalcoordinator,whopreparesthereportsforpartners includingWHO.ThesedataareincludedintheglobalHATAtlasbyWHOinaprocessthatinvolveschecksforcoherenceandconsistency.Anyverificationqueriesaresenttocountrycoordinatorsinordertomaximizedatavalidity.

EmphasisisgiventoestablishingandreportingthemostprobableplaceofinfectionofallHATcases,asthisinformationhasimportantepidemiologicalvalue.Allcasesdiagnosedinnon-endemiccountries(i.e.exportedcases)areincludedandmappedattheirmostprobableplaceofinfection,andthenationalfocalpointsareinformedaccordingly.

Surveillancedataareessential forplanning control andeliminationofHAT. Forexample, themappingoftransmissionareasbystratifiedlevelsofriskallowsthebestlocationofsentinelsitesandidentificationofareasthatarenotwellcovered.

CountrieshavecontributedsignificantlytothedevelopmentandupdatingoftheHATAtlasandhaveexpressedtheirinterestinusingthetoolatcountrylevel.CountrieshaveundergonetrainingandbeenprovidedwithequipmentandsoftwaretousetheAtlasfortheirbenefit.


8.4 Strategies for elimination: IEC (information, education, communication)

TheIECstrategyaimstoincreaseawarenessofr-HATamong:(i)exposedpopulations(i.e.onwheretoseekhealthcareandwhatprotectivemeasurestouse);(ii)health-careworkersaroundsentinelsites,toremainawareof r-HATasapossiblediagnosisandprovide informationtopatientsbeingreferred; (iii) traditionalhealers,astheyareoftenthefirstpeoplepatientsseekhelpfromandmustthereforebeincludedinapositivewaytoencouragepromptreferralofpatientspresentingHAT-compatiblesymptoms.

Thereisapotentialrolefortheprivatesectorinthisstrategy.Hotelsandparkshavealargestakeinprotectingtheiranimals,theirstaffandtheirvisitors,andhavetheresourcestopromotebetterawarenessofr-HAT.Iftransmissionareasincludenationalparks,messagingshouldberetargetedtothoseareasthattouristsmayvisitandhotelstaffmayfrequent.Astechnologyadvances,anthropologicalsurveyshavedemonstratedthatthecommunicationchannels thatpeopleusecurrentlyareverydifferent frompastmethods,e.g.mobiledevices.Suggestionsincludedasocialmediacampaignonthedangersofr-HATandprotectivemeasures,ortrainingprogrammesonprotectivemeasuresforhotelstaff.

There isalsoaneedtodelineatebetweenmessagingregardingprotectionof livestock (whichwasaverysuccessfulcampaign)andmessagingregardingwildlifereservoirsbecausethepopulationsatriskhaveverydifferent demographics (local residents versus tourists, respectively). Tourists aremore likely to travel tolargerhealth-carefacilitiessuchashospitals forearlydiagnosis,whereas localresidentsmayhave limitedaccesstohealthcareandsomessagingshouldfocusonthem.

8.6 Strategies for elimination: coordinationTheHATeliminationnetworkcoordinates theeffortsofawide rangeof stakeholdersagainstHAT (Figure 8.6.1). Its role is toconvenepartners inorder to identifygaps incontroleffortsand todevelopcommonstrategies forelimination.National coordinationbodiesarevery importantmembersof thenetwork thatevaluateprogressandplanactivitieswithintheendemiccountries.

Figure 8.6.1. TheHATeliminationnetwork

In the discussion, the importance of socio-anthropological aspects of r-HAT at the community level wasrecognized, including for theearlierdetectionof cases. Itwas recommended that this subject shouldbeaddressed.


9. Clinicalmanagementof importedeastAfrican trypanosomiasisin SouthAfrica:lessonslearnt

SouthAfricaisnotendemicforr-HAT,butcasesareregularlyimportedbymedicalevacuationflightsfromsouthandeastAfricancountries.Withmorethan60patientstreatedforr-HATinthepast18years,importantlessonsaboutclinicalmanagementcouldbelearnt.9Theexperiencewasgatheredinahighresourcesettingwithintensivecaremanagement;however,itcanbealsoadaptedforlesswell-resourcedareas.MostpatientsweretreatedinaprivatehospitalinJohannesburg.Ahospitalpharmacyrepositoryallows24-houraccesstomedicinesfreeofcharge.Telephoneconsultancyordeliveryofmedicinesforothermedicalfacilitiesabroadis also provided.

Moredetaileddataonthe20treatedcaseswerepresented.Mostpatientsweretourists; theothershadanoccupational-relatedexposure(Table 9.1).ThepatientsacquiredtheirinfectioninMalawi,Uganda,theUnitedRepublicofTanzania,ZambiaandZimbabwe(Table 9.2).

Table 9.1. Reasonsforexposureofimportedr-HATcasesinSouthAfrica,2004–2014

Table 9.2. Countrywheretheinfectionwasacquired

No. of cases (%)Foreigntourist 9Expatriate or resident 4Conservationist 2Game farmer 2Foreignsoldier,fieldexercise 1Pilot:touristtransport 1Church-relatedtravel 1TOTAL 20

Country of acquisition Number of cases and sites, 2004-2014Malawi 6(Kasungu3,Nkhotakota3)Zambia 6(LuangwaValley3,Kasanka2,Kafue1)Tanzania 3(Serengeti)Zimbabwe 3(Kariba1,ManaPools2)Uganda 2(QueenElizabethNationalPark,

?MurchesonFalls)TOTAL 20

Thethreekeyelementsforthediagnosiswereidentified:(i)exposureinanendemicarea;(ii)historyofapainfultsetsebite;and(iii)presenceoftrypanosomalchancre.Atrypanosomalchancrehasamarkedandpainfulerythema,butitsappearancevariesconsiderably(Figure 9.1).Achancreisnotalwayspresent(<50%ofcasesaccordingtotextbooks).Chancresareoftenmissed,especially inpartsof thebodythatarenotobviouslyvisibleoraremisinterpretedasinsectbitesorbacterialcellulites.AtrypanosomalchancreisusuallylargerandhasnoobviousnecrosisincontrasttoanescharinAfricantickbitefever.

9 FreanJ,SielingW,PahadH,ShoulE,BlumbergL.ClinicalmanagementofEastAfricantrypanosomiasisinSouthAfrica:Lessonslearned.IntJInfectDis.2018;75:101–8.doi:10.1016/j.ijid.2018.08.012.

https://doi.org/10.1016/j.ijid.2018.08.012


Figure 9.1. VariablepresentationsofeastAfricantrypanosomalchancres

Oneofthebiggestproblemsisadelayeddiagnosisthroughpoorhistory-taking,missingkeyclinicalsigns,delayedtransfer,incorrectapplicationofdiagnostictestsandinexperiencedlaboratorypersonnel.Insomeendemiccountries,localorexpatriatedoctorsmaynotbeawareofr-HAT,asitisaveryraredisease.Afterthe onset of symptoms, complicationsmaydevelop in less than 1week.Any extra delaymaybe criticaland result in severe disease,withmultiorgan involvement, severe thrombocytopenia, frequent bleeding,renalfailure,respiratorydistressandhepaticpathology,requiringhighlevelsofclinicalcare. Myocarditis was only observed in an individual case. Anotherratherearlycomplicationwasfluidoverload,whichmustbeconsideredinintravenousfluidmanagement.Onecasewithcomplicatedadrenalinsufficiencywaspresentedthathasbeendescribedonlyoncebefore.Decreasedlevelofconsciousnesswas inmostcasesnotasignofcentralnervoussystem(CNS)involvementandmayhaveotherexplanations,suchasmetabolicderangements.

Initially,trypanosomesmaybescantyanddifficulttodetectbymicroscopicexaminationofperipheralblood;therefore, blood smears should be repeated. Buffy coat filmshave an increased sensitivity, but they canbe technically challenging to produce (e.g. centrifugation needed). Every patient, irrespective of clinicalcondition,musthaveanexaminationofcerebrospinalfluid(CSF).InSouthAfrica,thisisusuallydoneafterafewdaysoftreatmentwithsuramin,whenthepatienthasclinicallyimprovedandtheperipheralbloodsmearisclearofparasites.Otherwise,false–positiveCSFfindingsfroma“bloodytap”maybepossibleandthereisatheoreticalriskofintroducingtrypanosomesintoCSF.TheresultsofCSFshouldbeinterpretednotonlyinisolationbutalsointheclinicalcontext;otherwise,theymayleadtooverdiagnosisofCNSinvolvement.

Treatmentisusuallystartedwithatestdoseofsuramin.Adversereactionsincludingcardiovascularcollapse,skinreactions,peripheralneuropathyandnephrotoxicitymayoccur.Onlytwopatientswereinthesecondstage and had to be treated with melarsoprol. Despite all the common problems described above, themortalityrateinthepresentedcaseserieswaslow(2/20;10%).

Successful case management relies on good laboratory facilities for rapid diagnosis, rapid access toantitrypanosomal treatment and skilled intensive care. Physicians in endemic countries are less and lessexperienced in the management of r-HAT. Besides operational research, recommendations should bedevelopedthatcanbeadaptedtolocalconditionsandespeciallyforlowresourcesettings.


10.Exportedcasesassurveillancetool for rhodesiense HAT

During2000–2018,atotalof138casesofHATwerereportedfromnon-endemiccountries(Figure 10.1).

Figure 10.1. Numbersofcasesofr-HATdiagnosedannuallyinnon-endemiccountries,2000–2018

Of thesecases,71%corresponded to the rhodesiense formand29%to thegambiense form.Amongther-HATcases,82%werediagnosedinthefirststageand18%inthesecondstage.Thevastmajorityofr-HATcaseswereintouriststravellingtoendemicareas(Table 10.1).

Table 10.1. Casesofr-HATdiagnosedinnonendemiccountriesaccording toactivityofthepatient,2000–2018

ActivityTourists 74Rangers 5Tourismworkers(guidespilots,lodgesstaff) 4Conservationistsworkers 3Soldiers 2Hunters 1Missionary 1Unknown 8Total 98


HAT cases were diagnosed in nonendemic countries in the five continents. In South Africa, a frequentdestination formedicalevacuationflights fromsouthandeastAfricancountries, thehighestnumber (31ofr-HATimportedcases)wasdiagnosed,followedbytheUnitedStates(20),theUnitedKingdom(12),theNetherlands(8),Belgium(4),Germany,India,Italy(3each),China,Norway,Sweden(2each)andArgentina,Brazil,Canada,France,Israel,PolandandSpain(1each).

The infectionwasmainly contracted inprotectedareas such asnational parks andwildlife reserves. Thecountryexportingthemost(47)r-HATcaseswastheUnitedRepublicofTanzania,mainlyfromtheSerengetiNationalPark.Forexample,aclusterofcasesthatoriginatedintheUnitedRepublicofTanzaniawassuggestiveofachangeinthelocalepidemiologyin2001.Theothercountriesexportingr-HATcaseswereZambia(20),Malawi(15),Zimbabwe(7),Uganda(7)andKenya(2).

During 2000–2018, some 1.7% of all cases was reported from nonendemic countries (Table 10.2). Theproportion of cases in whom r-HAT was diagnosed in nonendemic countries versus those diagnosed inendemiccountriesincreasedinthelastyears(2014–2018).Thevariousfactorsfortheincreasingproportionof r-HAT casesdiagnosed innon-DECswerediscussed.Underreporting inendemic countriesmaybeonefactor.Bettercontrolofthedomesticanimalreservoir,incontrasttoalackofcontrolofthewildlifereservoirintypicaltransmissionzonesfortourists,maybeanotherfactor.

Table 10.2. Casesofr-HATbycountryofinfectionandproportionofcasesdiagnosedinnonendemiccountries(exportedcases)during2000–2018(left)and2014–2018(right)

2000-2018 2014-2018Total Exported % Total Exported %

Kenya 40 2 5.0% 0 0Malawi 695 15 2.2% 119 4 3.4%Mozambique 2 0 0.0% 0 0Tanzania 1,660 47 2.8% 10 5 50.0%Uganda 3,281 7 0.2% 125 5 4.0%Zambia 137 20 14.6% 32 6 18.8%Zimbabwe 30 7 23.3% 8 0 0.0%Total 5,845 98 1.7% 290 20 6.9%

Whiletheriskof infection is lowforthetotalnumberof tourists, itcannotbedisregarded.Awareness inhealthstaffoftravelmedicineservicesoftheriskofHATisthusimportant.

As rapid access to antitrypanosomal treatment is crucial for patients,WHOmaintains strategic stocks invarious non-endemic countries and an emergency stock in Geneva, Switzerland (Figure 10.2). Country-specificregulationsfortheimportofmedicinesmustbeconsidered.TheirdistributionviatheWHOcountryofficesmaybehelpfultoavoiddelays.


Figure 10.2. AvailabilityofantitrypanosomalmedicinesfortreatmentofHATinnonendemiccountries

~ 1. WHO emergency stock of drugs in Geneva

~ 2. Strategic stocks of anti-trypanosomal medicines

¾ Hospital,RoyalLiverpool&BroadgreenNHSFoundationTrust,Liverpool(United Kingdom)

¾ UniversityCollegeLondon,NHSFoundationTrust,London(United Kingdom)

¾ FMHInnereMedizinundTropen-undReisemedizin,SwissTropical&PublicHealthInstitut,Basel(Switzerland)

¾ CentersforDiseaseControlandPrevention,Atlanta(USA)

¾ DivisionofInfectiousDiseases,InstituteofMedicalScience,Tokyo(Japan)

¾ UniversitairZiekenhuis,Antwerpen(Belgium)

¾ ErasmusMedicalCenter,Rotterdam(The Netherlands)

¾ HospitalClinic,Barcelona(Spain)

¾ NetcareMilparkHospital,Johannesburg(South Africa)

¾ NationalInstituteofParasiticDiseases,ChinaCDC,Shanghai(China)

¾ DepartmentofTropicalMedicine,MissioklinikWürzburg(Germany)

AntitrypanosomalmedicinesaredonatedbySanofiandBayeranddistributedsolelyundertheresponsibilityofWHO.Theycannotbeobtainedcommercially (except forpentamidine,which isused to treatdiseasesother thanHAT).Themedicinesareprovidedtocountries inwhich thedisease isendemic throughWHOcountryoffices,uponrequest,accordingtotheneedsandinformationprovided.TotreatHATcasesdiagnosedin nonendemic countries, pharmaceutical services should request themedicines fromWHOand provideepidemiologicalandclinicaldataoncasesinwhomthediseaseisdiagnosed.ThisinformationenablesWHOtomaintain anHAT surveillance system for nonendemic countries that provides valuable informationon“spots”oftransmissiontocomplementthedatacollectedinendemiccountries.Thisinformationisprovideddirectlytotheendemiccountriesandcanbeusedtotriggerspecificactivities.


11.Clinicaltrialfortreatment of rhodesiense HAT with fexinidazole

Fexinidazoleisthefirsteffectiveoralmonotherapyagainstbothstagesofg-HAT.ItreceivedapositivescientificopinionbytheEuropeanMedicinesAgencyinNovember2018,andmarketingauthorizationwasgivenintheDemocraticRepublicoftheCongoinDecember2018.

Theclinicaltrial(FEX07)isduetostartinMay2019andwillbeconductedinUgandaandMalawitoassesstheefficacyoffexinidazoleforr-HATpatients.

Fexinidazolecanbeconsideredaprodrugthatismetabolizedintofexinidazolesulfoxide(M1)andfexinidazolesulfone(M2).Theconcentrationof fexinidazolesulfone isdecisive forthetherapeuticeffect.Fexinidazolemustbetakenwithfood.Theplasmalevelsarehighestiftakenwithhighfatfood,buthighplasmalevelsarealsoreachedwithriceorplumpy-nut.ThepredictedCNSconcentrationlevels,with40%freefractionoffexinidazolesulfone,areclearlywithintherapeuticlevels.

Safety data are available from the pooled analysis of the threemain studies (FEX04, FEX05 and FEX06),including619patientswithg-HAT.Gastrointestinaldisorders,mainlyvomitingandnausea,andCNS-relateddisorders(headache,insomnia,tremor)werethemostcommonlyreportedadverseevents.Theincidenceofvomitingwashigherinthepaediatricstudy(FEX06)thanintheadultstudyandwasparticularlyhighintheloadingphaseofthetreatment(36%onday2,thetotalschedulebeing10days).Themajorityofpatientsvomitedmorethan2hafterdrugadministration,likelytriggeredatCNSlevel.Importantly,however,withtheexceptionof2patients,therewerenosevereeventsofvomitingandtreatmentcouldbecontinued.

TheHAT-r-ACCconsortium(ACCstandsforaccess)waspresented.CoordinatedbyDNDi with partners from France,Malawi,Portugal,Switzerland,andUganda,itsaimsare:(i)toextendtheindicationoffexinidazoleforthetreatmentofr-HAT(WP1);(ii)toensureproperexecutionoftheclinicaltrialthroughstrengthenedcapacityfortreatmentandcare(WP2);and(iii)toengagethelocalcommunitytoimproveaccesstotreatmentand extend case detection (WP3). The project management Committee (WP4) includes representativesfrom DNDi,InstitutdeRecherchepourleDéveloppement,theUniversityofLisbon,MakerereUniversityofUganda,MalawiMinistryofHealthandPopulation,theUgandaNationalHealthResearchOrganisation,theSwissTropicalandPublicHealthInstituteandEpicentre.Itwasemphasizedthatthetrainingsnotonlyservethetrialbutalsoenablecommunityengagementthroughlocalstaff.TheprogrammeismainlyfundedbytheEuropean&DevelopingCountriesClinicalTrialsPartnersip.


Protocolnumber: DNDi-FEX-07-HAT

Study title: Efficacy and safety of fexinidazole in patients with human African trypanosomiasis (HAT) due to Trypanosoma brucei rhodesiense: a multicentre, open-label clinical trial

Design: multicentre,open-label,non-randomized

Recruitmenttarget:34evaluablestage-2r-HATpatients(stage-1patientswillbeincludedbutdonotinfluencethestatisticalanalyses)

Studysites:LwalaHospital(Uganda)andRumphiDistrictHospital(Malawi).

Patients from neighbouring health centres: Kaberamaido/Dokolo districts (Uganda) and Rumphi/Mzimba Northdistricts(Malawi)andChama(Zambia)willbetransportedtothesitesfortreatment

Studyduration:2yearsrecruitmentand1-yearfollow-up

Maininclusioncriteria

~ Signedinformedconsentform

~ ≥6yearsold

~ ≥20kgbodyweight

~ Abilitytoingestatleastonecompletemealperday

~ Karnofskyindex≥40

~ ParasitologicalconfirmationofT. b. rhodesienseinfection

~ Havingapermanentaddressorbeingtraceablebyothersandwillingandabletocomplywithfollow-upvisitschedule

~ Agreementtobehospitalizedforaminimumof11daysandtoreceivethestudytreatment

Mainexclusioncriteria

~ Active clinically relevant medical conditions other than HAT that may jeopardize subject safety or at theinvestigator’sdiscretionmayinterferewithparticipationinthestudy

~ Compromised general health or severely deteriorated general condition, such as severe malnutrition,cardiovascularshock,respiratorydistressorterminalillness

~ Patientswithseverehepaticimpairment

~ Firsttrimesterofpregnancy

~ Anycontraindicationtonitroimidazoleclass(knownhypersensitivity)ortoanyoftheexcipients

~ Patientspreviouslyenrolledinthestudyorhavingalreadyreceivedfexinidazole

Treatment:fexinidazole10days(sameregimenasing-HAT),in2phases ~ 2dosesdependingonthepatient’sageandweight:

~ Alladultsandchildren(≤15yearsold)≥35kg:

¾ D1toD4(1800mg/day)


~ Childrenweighing≥20and<35kg:



Followupvisits:after1month,9weeks,6monthsand12monthsTestofcureat6and12monthsincludingthick/thinbloodsmearand/orlymphnodeaspiratemicroscopicexamination,lumbarpunctureforparasitedetectionandCSFwhitebloodcellcount.


Theinitialdataareexpectedforthebeginningof2021anditisenvisagedthatthefinalresultswillbemadeavailableinthesecondquarterof2023.

Inthediscussion,aregularupdateonprogressofthestudywasproposed(e.g.atthenext(fourth)stakeholdersmeeting).Someparticipantssharedtheiroptimisminreachingtherecruitmenttarget,astheclinicaltrialwillraise awareness of the disease.

Thepotentialofacoziborole,asingleoraldosetreatment,wasalsodiscussed.Theclinicaltrialrecruited206patientsinstages1and2ofg-HAT,mostoftheminlatestage2,andwascompletedinMarch2019.InApril2014,about30%ofpatientshadcompletedthefollowupperiodof18months.Theabsorptionofacoziboroleis less dependent on food than that of fexinidazole.


12.OneHealth:linkingeliminationof rhodesiense HAT with other initiatives

12.1 Epidemiological studies in animals and tsetse flies, and new molecular approaches in Zambia

Luapulaprovince, inthenorthofZambia,borderingtheDemocraticRepublicoftheCongo,wasahistoricfocusof r-HAT,withnoreportedhumancasessince2000.However,after2casesof r-HATwerereported(in2017and2018),abiologicalsurveywasconductedincattleatthelocationofthelastcase(inSamfya).Bloodfrom40cattlewasanalysedwithPCR(LAMP)fortrypanosomes,yieldingpositiveresultsfortsetse-transmittedanimaltrypanosomes,butnotforhumaninfectiveforms.

Astudycombiningmicroscopyandmoleculartechniquesdeterminedthepresenceoftrypanosomespeciesin cattle, goats and tsetseflies in the Luangwavalley, north-easternZambia,butdidnot identify speciesinfectivetohumans.Some10furthertsetsesurveysinnorthernandcentralZambiafoundsamplespositiveforserum-resistanceassociatedprotein(SRA)(invaryingproportions),indicativeforT. b. rhodesiense,mainlyin Glossina morsitans,themainvectorforr-HAT(Figure 12.1.1).Astheseareasarecurrentlyconsideredatlow,verylowornoriskoftransmission,theneedforsurveillanceofHATintheseareaswassuggested.

As the currently available tsetse traps are ineffectiveagainstG. morsitans, anewmobile, carmountabletrap(“SugimotoTrap”)wasdeveloped.Thetrapiseasytoproduceatlowcostandminimizesexposuretofliesduringoperation.ThetrapwastestedinvariousnationalparksinZambiaandMalawiandfoundtobeeffectiveagainstG. morsitans, G. pallidipes and G. brevipalpes.

10 LaohasinnarongD,GotoY,AsadaM,NakaoR,HayashidaK,KajinoKetal.StudiesoftrypanosomiasisintheLuangwavalley,north-easternZambia.ParasitVectors.2015;8:497.doi:10.1186/s13071-015-1112.

https://doi.org/10.1186/s13071-015-1112-y


Figure 12.1.1 Proportionofserum-resistanceassociated(SRA)polymerasechainreaction(PCR)-positivetsetsefliesinvariousareasinZambia,indicatingpresenceofT.b.rhodesienseandpossibleriskof

transmissiontohumans

To improve epidemiological knowledge of African trypanosomiasis, better tools are required tomonitortrypanosome genotypes circulating in both mammalian hosts and tsetse fly vectors. Genotyping oftrypanosome species is possible. A single test approach for accurate, sensitive detection and taxonomiccharacterizationoftrypanosomesbycomprehensiveanalysisofinternaltranscribedspacer1ampliconswaspresented.11Bloodmealanalysisoftsetsefliesshowedthatfliescanbloodfeednotonlyfromcommonhostssuchaswarthog,kudu,buffalo,human,orcattle,butalsofromfruit-batsandrodents.

Inthediscussion,exchangewithothergroups(fromFAO/IAEAdivision)workingonmobiletsetseflytrapswasencouraged.TheimportanceofmappingtheabsenceofT. b. rhodesiensewasacknowledged.

12.2 Tsetse control and the management of r-HATTherearedifferenttsetseflycontrolstrategies.Forexample,groundsprayingisextensivelyusedinZimbabweand aerial spraying in Botswana. In central and southernUganda, cattle are insecticide treatedwith therestrictedapplicationprotocoltocontrolr-HAT(StampingOutSleepingSicknesscampaign).However,manyr-HATfociineastandsouthernAfricaareassociatedwithwildernessareas,wherethiscontrolmethodcannotbeapplied.Smallinsecticide-treatedtargets(“tinytargets”)aredeployedover4000km2ofnorthernUganda(endemicareasforg-HAT)andsuppressedthetsetsepopulationby>80%formorethan4years.Tinytargetsarenotascost–effectiveagainstsavannahtsetsefliesandhencethismethodisappropriateonly inareaswhere T. b. rhodesienseistransmittedbyG. f. fuscipes.Larger,traditionaltrapsareusedinKenya,Malawi,theUnitedRepublicofTanzania,ZambiaandZimbabwe.Table 12.1 showstheseveralcompetentvectorspeciesofHATwiththeirvariabledistributionsacrossendemiccountries.

11 GaithumaAK,YamagishiJ,MartinelliA,HayashidaK,KawaiN,MarselaM,etal.AsingletestapproachforaccurateandsensitivedetectionandtaxonomiccharacterizationofTrypanosomesbycomprehensiveanalysisofinternaltranscribedspacer1amplicons.PLoSNeglTropDis.2019;13(2):e0006842.doi:10.1371/journal.pntd.0006842.

https://doi.org/10.1371/journal.pntd.0006842


Table 12.1. CompetentGlossinavectorsofHATandnumbersof reportedhumancasesbyendemiccountry

Country Primary vectors Other vectorsHAT cases

2000–2009HAT cases

2010–2017

Uganda G. f. fuscipes Morsitansgroup 2848 431Malawi G. morsitans 471 209Zambia G. morsitans, G. pallidipes 82 50Zimbabwe G. morsitans, G. pallidipes 6UnitedRepublicofTanzania

G. swynnertoni, G. pallidipes Palpalisgroup 14 24

Kenya G. swynnertoni, G. pallidipes Palpalisgroup 38 2

Geostatisticalmodelsusing remotely-senseddatahavepotential to identify sitesof relativelyhighvectorabundance,forsurveillanceandcontrol,beyondthespatialextentofinitialsampling.12

Inafieldinvestigation,tsetseandT. b. rhodesiense wereunexpectedlyscarceinanareaoutsidetheSerengetiNationalPark,wheretheywerepredictedtobeabundant.Anexplanationwasthefrequentuseofinsecticidetreatmentsagainstticksandtsetsefliesbylivestockkeepers.Asimulationmodelhasbeendevelopedshowingtheimpactofinsecticide-treatedcattledependingonthefrequencyofuse. Interventionsbylivestockkeepersoncattleand thewiderenvironmentare reducing theabundanceof tsetse in farmingareasand therebyreducingtheriskofr-HAT.Afurthersimulationmodelhasbeendevelopedthatallowstheimpactofvariouscontrol interventions to be predicted. Even a limited deployment of targets around the edge of VwazaNationalPark(Malawi)waspredictedtoreducetheriskofHAT.

AsimulationmodelhasbeendevelopedtotestwhetherrecentincreasesintemperatureintheManaPoolsNationalParkoftheZambeziValleyofZimbabwecouldaccountforthesimultaneousdeclineoftsetseflies.13 Themodelsuggeststhattheincreaseintemperaturemayexplaintheobserveddecreaseoftsetseflies.Itprovidesafirststepinlinkingtemperaturetotrypanosomiasisrisk.Conversely,newdiseasefocimayemergewithallocationoffliesinhigher,previouslycoolerregions.

A guidance document on tsetse fly control tools, specifying idealmeasurements, colours,materials anddeploymentmethods in different environments tomake them fit for purpose is needed to enhancetheimplementationandefficacyof these tools.Aworking groupof tsetse control practitioners across g-HATandr-HATendemiccountriesaswellasWHOsupport forvectorcontrol recommendationswasthereforerequested.

12.3 Overview of PATTEC activities in East and South AfricaGenerally,State-drivenvectorcontrolactivitiesaimfor large-scaleoperations.Tsetseandtrypanosomiasiscontrolinterventionsareoftenstandalone,unattractivetodonorsand,inrecentyears,unfunded.Interventionsaretakingplace inselectedareas.Packagingofproposalstoaddressbroaderaspects isrecommendedtoattractdonorfunding.

AbriefoverviewofvectorcontrolactivitiesineastandsouthAfricancountrieswasgiven.

12 LordJS,TorrSJ,AutyHK,BrockP.Geostatisticalmodelsusingremotely-senseddatapredictsavannatsetsedeclineacrosstheinterfacebetweenprotectedandunprotectedareasinSerengeti,Tanzania.JApplEcol.2018;55(4):1997–2007.doi:10.1111/1365-2664.13091.

13 LordJS,HargroveJW,TorrSJ,ValeGA.ClimatechangeandAfricantrypanosomiasisvectorpopulationsinZimbabwe’sZambeziValley:Amathematicalmodellingstudy.PLoSMed.2018;15(10):e1002675.doi:10.1371/journal.pmed.1002675.

https://doi.org/10.1371/journal.pmed.1002675


Uganda:thelastlarge-scaleoperationendedin2012.Anumberoffollowupproposalsarenotyetfunded.Trapsandtargets,andcattlesprayingaredeployedinselectedareas.VectorcontrolactivitiesaredonebypartnersinselectedHAThotspots.

South Sudan: thepoliticalinstabilityishinderinginitiationofvectorcontrolactivities.

United Republic of Tanzania:lowlevelvectorcontrolactivities(networkofdiptanks)areundertaken;largescaleoperationsarenotfunded.Anationaltsetseandtrypanosomiasiscontrolstrategyisunderdevelopment.

Kenya: thelastlarge-scaleoperationsconcludedin2012–2013.ICIPEispromotingrepellenttechnologyinselectedareas.KenyaisapparentlyfreeofHAT(butthisstatusisquestionableintheMasaiMara–Serengetiecosystem).

Rwanda:therearelimitedvectorcontrolactivitiesinAkageraNationalPark.ThelastcaseofHATwasin1998.

Burundi:therearevirtuallynovectorcontrolactivities.TheHATstatusisnotdefined.

Zimbabwe: vectorcontrolactivitiesarewelladvanced.

Zambia:vectorcontrolisprogressingwellwithgovernmentalcommitment(e.g.aerialspraying).

Botswana and Namibia:bothcountriesareapplyingforregistrationtobetsetsefree.

Theintensityofvectorcontrolactivitiesvariesgreatlyacrossregions.Large-scalevectorcontroloperationsfacechallengestofunding.GovernmentsshouldconsidertargetingvectorcontrolinareasofHATtransmission,alsotoassessthecontributionofvectorcontroltoHATelimination.Awareness/advocacyforvectorcontrolshouldberaisedatthehighestpoliticallevel.

APATTECcommunication/advocacystrategy,preparedandsupportedbyIAEA,targetspoliticalplayersatthehighestlevel.ThereisincreasedengagementwithRegionalEconomicCommunitiesadvocatingforregionalprogrammes.Recently,meetingshavebeenheldwiththeEastAfricanCommunity,theEconomicCommunityofWestAfricanStatesandtheEconomicCommunityofCentralAfricanStates.

SpecializedTechnicalCommitteesandtheStatutoryMinisterialForumonAgriculture,RuralDevelopment,WaterandEnvironmentareplatformsfromwhichpoliticalawarenesscanbeenhancedandrecommendationsthenmadeto theExecutiveCouncil fordecisionsofAfricanHeadsofStateandGovernment.SideeventsheldduringsummitsoftheAfricanUniononthematicissues,retreatswithpoliticiansonthematicissues,briefingsessionsofthePermanentRepresentativeCommitteeandwithAmbassadorsofMemberStatesoftheCommitteeoftheAfricanUnion,whichreporttonationalcapitalsontheoutcomesofbriefingsessions,offerfurtherpossibilitiestoraiseawareness.

Aproposedway forward is collaborationamongPATTEC,WHOandotherpartnerson thepreparationofpolicybriefs onHATelimination.SummitdecisionsinformedbypolicybriefscouldcommitAfricanHeadsofStateandGovernmenttotheHATeliminationstrategy.

Inthediscussion,thehighlyeffectiveprogrammesinEthiopiaandSenegalwerementioned,whichusethesterileinsecttechniquefortsetsecontrol.ThePATTECdeclarationof2001ontheeradicationofthetsetseflyisbeingreviewed,althoughlimitedstaffinginthePATTECcoordinationofficemakesthistaskchallenging.


12.4 FAO and PATT: the progressive control pathway (PCP) for African animal trypanosomosis

TheProgrammeAgainstAfricanTrypanosomosis(PAAT)wasofficiallyestablishedinNovember1997bythe29thSessionoftheFAOConference(resolution5/97).Aninteragencycollaboration,PAATcoordinatestheworkofFAO,WHO,theIAEAandtheInter-AfricanBureauforAnimalResourcesoftheAfricanUnion.

ThevisionofPAATisanAfricancontinentwheretrypanosomosesnolongerconstrainsustainableagricultureandruraldevelopment,northreatenhumanhealth.PAATisfundedbyaregularbudgetfromFAO,anannualcontributionfromWHO(forworkontheHATAtlas)andextrabudgetarycontributionstoFAO(includingfromtheGovernmentofItaly).

PartnersofPAATareAU-PATTEC,AfricanMemberStatesaffectedby tsetseand trypanosomiasis (38sub-Saharancountries),OIE,theInternationalFundforAgriculturalDevelopmentandtheUnitedNationsIndustrialDevelopmentOrganization. There are international cooperations for development and cooperationswithcivilsociety(ItalianCooperation,UnitedKingdomDepartmentforInternationalDevelopment,GlobalAllianceforLivestockVeterinaryMedicines).PartneringresearchinstitutesarebasedinAfrica(CentreInternationalde Recherche-Développement sur l’Elevage en Zone Subhumide, ICIPE, International Livestock ResearchInstitute,NationalAgricultureResearchSystemsandacademia)aswellasinEurope(IRD/CIRAD[CooperationInternationaleenRechercheAgronomiquepourleDéveloppement],ITM).HealthforAnimals(formerlytheInternationalFederationforAnimalHealth)isaprivate-sectorpartner.

FAOpromotestheprogressivecontrolpathway(PCP)forAATasastrategicframeworktoreducethediseaseburden.ItalsopromotesOneHealthinterventions(e.g.livestockprotectivefences).TheAtlasesoftsetseandAAT(i.e.continentalandnational)havebeendeveloped,andWHOissupportedintheAtlasofHAT.Capacitydevelopment and technical support for endemic countries is provided, as well as knowledge products(e.g.publications,website,news,seminars,supporttoresearch,etc.).

WhilegreatstrideshavebeenmadeintheeliminationofHAT,progressinthecontrolofAATlagsbehind.PCPsareusedforthecontrolofanumberofhumanandanimaldiseases,e.g.peste de petits ruminents, brucellosisandrabies.InternationalorganizationssuchasFAO,WHO,OIEandAUrelyonPCPframeworkstoplan,implementandevaluateinterventions.TheoperationaldevelopmentofaPCPforAAT14wasledbyFAO(intheframeworkofPAAT),incollaborationwithIAEA,AU-PATTECandCIRAD,andinconsultationwithOIEandWHO.PCPisastepwiseapproachoffivestagesplusapre-entry(“belowstage1”)level(Figure 12.4.1).Progressionfromonestagetoanother ispossibleonly if thesetgoalsaremetandthefollowingstage isprepared.Anindependentvalidationofstageprogressionisrequired.

At the pre-entry level, political commitment and a functioning specialized national structure with corecapacitiesthatismandatedtodealwithtsetseandAATareessentialrequirementsforenteringPCP.Instage1,affectedcountriesdeveloptechnicalcapacitiesandgainsufficientunderstandingofAATdistribution,riskandimpactforevidence-basedplanningofsubsequentactivities.Pilotfieldinterventionsarealsoconducted.Larger scalefieldactivitiesare implemented in stage2andbeyond. Stage2aims toachieve sustainable,economically-profitable reductions in AAT burden. The intervention strategy is based on integratedmanagementofAAT(acommunity/farmer-basedapproach).Theaimofthefinalstages(3–5)ofPCPistocreatesustainableAAT-freeareas.Stage3 iscompletedwhenAATtransmission is interrupted. Instage4,somecontrolmeasuresaremaintained,whileinstage5theeliminationofAATmustbesustainableintheabsenceofinterventions.

14 DiallO,CecchiG,WandaG,ViljoenGJ,MattioliR,BouyerJ,etal.DevelopingaprogressivecontrolpathwayforAfricananimaltrypanosomosis.TrendsParasitol.2017;33(7):499–509.doi:10.1016/j.pt.2017.02.005.

https://doi.org/10.1016/j.pt.2017.02.005


Figure 12.4.1. Theprogressivecontrolpathway(PCP)forAfricananimaltrypanosomiasis(AAT)

Duringthe17thAU-PATTECCoordinators’Meeting(26–28November2018)itwasrecommendedthatthePCPconceptbestreamlinedintonationalandregionalstrategiesandprojectsagainstAAT.Stakeholdershavebeen engaged in threeAU-PATTECmeetings aswell as in severalworkshops inAAT-affected countries ineasternAfricasince2015.

AAT isanOIEnotifiabledisease.There isnoofficial recognitionbyOIEof “freedomfromAAT”;however,countryself-declarationsoffreedomarepossible.ThefirstAAT-specificchapterintheOIETerrestrialCodewillprovideanopportunitytocloseagapforAAT.FAOsupportsthiseffortandparticipatesinmeetingswithaviewtoensuringconsistencywithPCP.

Inthediscussion,thepossibilityofMemberStatesapplyingforfundingofsmall-scaletechnicalprojectsviatheFAOcountryrepresentativewasraised.


13.ConclusionsTheparticipantsofthethirdstakeholdersmeetingconcludedasfollows.

1. Thelownumberofreportedr-HATcasesindicatesthatthegoalofeliminationofHATasapublichealthproblemby 2020 iswithin reach.Nevertheless, under-detection remains a concern and surveillanceshould be reinforced in response.WHOmaintains its commitment to supporting countries endemicforthediseaseinensuringaccesstodiagnosisandtreatmentforr-HATpatientsandinmonitoringtheepidemiologicalprogressionofthedisease.

2. Wildlifeanddomesticanimalsconstitutethemainreservoirsofr-HATandplayacentralroleinmaintainingtransmissiontohumansthroughthebiteofinfectioustsetseflies.Inthisepidemiologicalcontext,vectorcontrolshouldbestrengthenedandanimalhealthinterventionsdeployedinaOneHealthframeworkto attain r-HAT elimination. Theuseof theprogressive control pathway approach forAfrican animaltrypanosomiasiscouldbeusefulinpromotingsynergiesforcontroloftheanimalreservoirandthevector.

3. Given the variability in the characteristics and quality of vector control tools, guidelines should bepreparedtoensurethequalityandgooduseofvectorcontroltoolstailoredtodifferentenvironments.

4. New tools for r-HAT diagnosis and surveillance that can be adapted for use in the field should bedevelopedasapriority.

5. Thewidespreaduseofrapiddiagnostictestsformalariahasreducedtheuseofbloodsmearmicroscopyand thereby diminished the probability of diagnosing r-HAT. Therefore, in areas endemic for r-HAT,clinicalandlaboratoryalgorithmsincludingbloodsmearmicroscopyshouldbedesignedandappliedfordiagnosisofr-HAT.

6. Progresshasbeenmadeinthepossibleintroductionofnewtreatmentsforr-HAT.Fexinidazolehasbeenapprovedfortreatmentofgambiense-HATandaclinicaltrialisexpectedtostartshortly.Updatesonthistrial shouldbepresentedat thenext (fourth) stakeholdersmeeting.Anewstage-independent singledoseoraltreatmentwithacoziborolecouldofferotherpossibilitiesfortreatment.

7. Advancesintheprocessofvalidationofeliminationofr-HATasapublichealthproblemhavebeenmade,andeligiblecountriesareencouragedtoapplyforvalidation.WHOshouldmakepubliclyavailablethematerialithasdeveloped,includingtemplatesforcountrydossiers,aswellastheproceduresandcriteriaforassessingthem.ThismaterialcouldalsobeusedtoraiseawarenessofHATandcouldrepresentablueprintforotherdiseasestargetedforeliminationtofollow.

8. Thesignificant fundinggap in control, researchandawareness-raisingactivitiescalls foradvocacybyexternaldonors;nationalappropriationincludingdomesticfinancingiscriticalalsoforsustainabler-HATelimination.

9. Thegapsindiagnostic,treatmentandvectorcontrolcapacities,mainlyintermsoftrainedstaff,togetherwith the loss of expertise and frequent rotation of skilled personnel, areworrisome and should beaddressed.Possiblesolutions includeengaginghealthauthoritiessubnationallyandoptimizingexpertresourcesnationallyandinternationally,includingincascadetraining.

10. Aidmaterialsandmanualsforimprovementofpatientmanagementinendemicareasandofexportedcasesshouldbeprepared.

11. r-HATactivitiesshouldbeintegratedintootherhealthprogrammesasameansofreinforcingcontrolandsurveillanceofr-HAT.

12. The importantsocio-anthropologicalaspectsof r-HATat thecommunity level, includingthepotentialfacilitation of earlier detection of cases and access to treatment, should be addressed alongsidesurveillanceandcontrolactivities.

13. r-HATstakeholdersareencouragedtoengagedintheongoingprocessofdevelopingindicators,targetsand milestones for the new NTD roadmap 2021–2030.


Annex1.Agenda

Day 1 – Wednesday 10 April 2019: Description of the situation of HAT and progress

09:00–09:30 Welcome WHOAFRORepresentative Director,WHO/CDS/NTD

09:30–09:45 Introduction to the meeting Coordinator,WHO/CDS/IDM Chairperson

10:00–11:00Global situation of r-HAT

WHOReview of the conclusions of the previous meeting

11:00–13:00

Country report on r-HAT–Kenya – Malawi –UnitedRepublicofTanzania – Rwanda –Uganda – Zambia – Zimbabwe

Focalpointsofeachcountry(R.Kisati,M.Lemerani,J.B.Minja,J.B.Mbonigaba,C.Wamboga,V.Mwanakasale,P.Manangazira)

14:00–16:00

Elimination of rhodesiense HAT as a public health problem in 2020

HATeliminationTechnicalAdvisoryGroup(HAT-e-TAG):specificr-HATaspects V.Lejon

Eliminationofr-HATasapublichealthproblembycountries

–Dossierofelimination –Validationofelimination –Countriesstatus

WHO

NTDroadmap2030:target2030(indicatorsandtargets) WHO

16:00–17:00

Strategies for elimination. Reinforced integrated surveillance:

–Selectionofsites –Capacity-buildingindiagnosisandtreatment –Managementofdrugs –Monitoringandevaluation –Reporting

WHO

Day 2 – Thursday 11 April 2019: Control and elimination of r-HAT

09:00–09:30 Clinical management of complicated cases of HAT Case management protocols L.Blumberg

09:30–10:00 Exported cases as a surveillance tool for HAT WHO10:30–12:30 Clinical trial for treatment of r-HAT with fexinidazole NStrub,ATarral,O.Valverde

13:30–15:00

Contribution of other sectors to r-HAT elimination (One Health): linking elimination of r-HAT with other initiatives:

–Vectorcontrol – Animal health –Managementofprotectedareas

FAO/PATTEC/COCTU Openfloor

15:00–16:00 Gaps and challenges Generaldiscussion16:00–17:00 Conclusions, outcomes and closure of meeting Generaldiscussion


Annex2.Listofparticipants

Members

ProfessorM.Barrett,1UniversityofGlasgow,Glasgow,Scotland,UnitedKingdom

DrJ.Bernard,MinistryofHealth,CommunityDevelopment,Gender,ElderlyandChildren,Dodoma,UnitedRepublicofTanzania

DrS.Biéler,FoundationforInnovativeNewDiagnostics,Geneva, Switzerland

ProfessorL.Blumberg,CentreforEmergingandZoonoticDiseases,Johannesburg,SouthAfrica

DrP-MBorne,1CevaSantéAnimaleS.A.,Libourne,France

ProfessorC.Burri,SwissTropicalandPublicHealthInstitute,Basel,Switzerland

ProfessorP.Buscher,1InstituteofTropicalMedicine,Antwerp,Belgium

DrG.Cecchi,FoodandAgricultureOrganizationoftheUnitedNations,Rome,Italy

DrU.Dietmar-Madeja,1BayerHealthCarePharmaceuticals,Berlin,Germany

DrG.Doll,Sanofi,Gentilly,France

DrB.Fatunmbi,1WHORepresentative’sOffice,Kampala,Uganda

ProfessorE.Fèvre,UniversityofLiverpool,Neston,UnitedKingdom

Dr R. Grais,1Epicentre,Paris,France

MrR.ArgilesHerrero,1InternationalAtomicEnergyAgency,Vienna,Austria

Dr G. Hesse,1 BayerEnvironmentalScience,Ecully,France

MrsR.Kasati,1MinistryofHealth,Nairobi,Kenya

DrV.Lameyre,Sanofi,Gentilly,France

DrV.Lejon,ResearchInstituteforDevelopment,Montpellier,France

MrM.Lemerani,MinistryofHealth,Lilongwe,Malawi

DrA.Lidner,InstituteofTropicalMedicineandInternationalHealth,Berlin,Germany

DrP.Managazira,MinistryofHealthandChildWelfare,Harare, Zimbabwe

ProfessorI.Maudlin,1 UniversityofEdinburgh,Edinburgh,Scotland,UnitedKingdom

DrL.Matemba,NationalInstituteforMedicalResearch,DaresSalaam,UnitedRepublicofTanzania

DrE.Matovu,MakerereUniversity,Kampala,Uganda

MrJ.BoscoMbonigaba,MinistryofHealth,Kigali,Rwanda

Mr A. Mortensen,1VestergaardSA,Lausanne,Switzerland

DrK.Msyamboza,1 WHORepresentative’sOffice,Lilongwe,Malawi

DrV.Mwanakasale,CopperbeltUniversitySchoolofMedicine,Ndola,Zambia

ProfessorB.Namangala,UniversityofZambiaSchoolofVeterinaryMedicine,Lusaka,Zambia

Dr A. Nanai, 1 WHORepresentative’sOffice,DaresSalaam,UnitedRepublicofTanzania

ProfessorJ.Ndung’u,FoundationforInnovativeNewDiagnostics,Geneva,Switzerland

DrM.D.Ngamije,WHORepresentative’sOffice,Kigali,Rwanda

Dr E. Hernandez Pando,1MerialRwd,Lyon,France

MrF.Petit,1 MerialRwd,Lyon,France

DrA.Picado,FoundationforInnovativeNewDiagnostics,Geneva, Switzerland

DrC.L.Schumacher,1MerialRwd,Lyon,France

DrJ.B.A.Seixas,UniversidadeNOVAdeLisboa,Lisbon,Portugal

DrW.Shereni,MinistryofAgriculture,MechanizationandIrrigationDevelopment,Harare,Zimbabwe

DrP.Solano,InstitutdeRecherchepourleDéveloppement,Montpellier,France

DrP.Songolo,WHORepresentative’sOfficeforZambia,Lusaka,Zambia

Dr M. Steele,1 Bill&MelindaGatesFoundation,Seattle,UnitedStatesofAmerica

DrN.Strub-Wourgaft,DrugsforNeglectedDiseasesinitiative, Geneva, Switzerland


ProfessorC.Sugimoto,HokkaidoUniversity,Sapporo,Japan

Dr L. Tano,1MerialSASVeterinary,Lyon,France

DrA.Tarral,DrugsforNeglectedDiseasesinitiative, Geneva, Switzerland

MrI.Tirados,LiverpoolSchoolofTropicalMedicine,Liverpool,UnitedKingdom

ProfessorS.Torr,LiverpoolSchoolofTropicalMedicine,Liverpool,UnitedKingdom

Professor C. Waiswa,1MinistryofAgricultureAnimalIndustryandFisheries,Kampala,Uganda

DrC.Wamboga,MinistryofHealth,Kampala,Uganda

DrG.WisemanWanda,AfricanCommission,AddisAbaba, Ethiopia

ProfessorS.Welburn,1 UniversityofEdinburgh,Edinburgh,Scotland,UnitedKingdom

DrO.Valverde,DrugsforNeglectedDiseasesinitiative, Geneva, Switzerland

DrM.J.B.Vreysen,1InternationalAtomicEnergyAgency,Vienna,Austria

DrW.Zhao,FoodandAgricultureOrganizationoftheUnitedNations,Rome,Italy

DrG.BinghamZivanovic,1VestergaardFrandsenSA,Lausanne,Switzerland

Secretariat

DrB.Abela-Ridder,NeglectedZoonoticDiseases,DepartmentofControlofNeglectedTropicalDiseases,WorldHealthOrganization,Geneva,Switzerland

DrD.ArgawDagne,Innovative&IntensifiedDiseaseManagement,DepartmentofControlofNeglectedTropicalDiseases,Geneva,Switzerland

Dr A. Diarra,1 WHORepresentative’sOffice,Libreville,Gabon

DrA.KadimaEbeja,WHORepresentative’sOffice,Kinshasa,DemocraticRepublicoftheCongo

DrL.Grout,1 Innovative&IntensifiedDiseaseManagement,DepartmentofControlofNeglectedTropicalDiseases,WorldHealthOrganization,Geneva,Switzerland

DrM.NtuliMalecela,DepartmentofControlofNeglectedTropicalDiseases,WorldHealthOrganization,Geneva, Switzerland

DrJ.R.FrancoMinguell,Innovative&IntensifiedDiseaseManagement,DepartmentofControlofNeglectedTropicalDiseases,WorldHealthOrganization,Geneva,Switzerland

DrR.Minghui,HIV/AIDS,Tuberculosis,MalariaandNeglectedTropicalDiseases,WorldHealthOrganization,Geneva, Switzerland

DrG.Priotto,Innovative&IntensifiedDiseaseManagement,DepartmentofControlofNeglectedTropicalDiseases,WorldHealthOrganization,Geneva,Switzerland

DrP.P.Simarro,Consultant,Geneva,Switzerland

Report of the third WHO stakeholders meeting

on rhodesiense human African trypanosomiasis


report of the third who stakeholders meeting on

Documents