Nifurtimox plus Eflornithine for Late-Stage Sleeping Sickness in Uganda A Case Series 英文参考文献.docVIP

NifurtimoxplusEflornithineforLate-StageSleeping SicknessinUganda:ACaseSeries FrancescoChecchi1,2,PatricePiola1,HarrietAyikoru3,FlorenceThomas1,DominiqueLegros1,4 ,Gerardo Priotto1* 1Epicentre,Paris,France,2DepartmentofInfectiousandTropicalDiseases,LondonSchoolofHygieneandTropicalMedicine,London,UnitedKingdom,3Me′decinsSans Frontie`res, Frenchsection,Paris,France,4AlertandResponseOperations,EpidemicandPandemicAlertandResponse,WorldHealthOrganization,Geneva,Switzerland Abstract Background: We report efficacy and safety outcomes from a prospective case series of 31 late-stage T.b. gambiense sleepingsickness(HumanAfricanTrypanosomiasis,HAT)patientstreatedwithacombinationofnifurtimoxandeflornithine (N+E)inYumbe,northwestUgandain2002–2003,followingonapreviouslyreportedterminatedtrialinnearbyOmugo,in which17patientsreceivedthecombinationunderthesameconditions. Methodology/Principal findings: Eligible sequential late-stage patients received 400mg/Kg/day eflornithine (Ornidyl, Sanofi-Aventis)forsevendaysplus15mg/Kg/day(20mgforchildren,15yearsold)nifurtimox(Lampit,BayerAG)forten days. Efficacy (primary outcome) was monitored for 24 months post discharge. Clinical and laboratory adverse events (secondaryoutcome)weremonitoredduringtreatment.All31patientsweredischargedalive,buttwodiedpost-discharge ofnon-HATandnon-treatmentcauses,andonewaslosttofollow-up.Efficacyrangedfrom90.3%to100.0%accordingto analysisapproach.Fivepatientsexperiencedmajoradverseeventsduringtreatment,andneutropeniawascommon(9/31 patients). Conclusions/Significance: Combined with the previous group of 17 trial patients, this case series yields a group of 48 patientstreatedwithN+E,amongwhomnodeathsjudgedtobetreatment-orHAT-related,notreatmentterminationsand no relapses have been noted, a very favourable outcome in the context of late-stage disease. N+E could be the most promisingcombinationregimenavailableforsleepingsickness,anddeservesfurtherevaluation. Citation: Checchi F, Piola P, Ayikoru H, Thomas F, Legro