Early Prediction of Treatment Efficacy in Second-Stage Gambiense Human African Trypanosomiasis 英文参考文献.docVIP

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Early Prediction of Treatment Efficacy in Second-Stage Gambiense Human African Trypanosomiasis 英文参考文献.doc

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Early Prediction of Treatment Efficacy in Second-Stage Gambiense Human African Trypanosomiasis 英文参考文献

EarlyPredictionofTreatmentEfficacyinSecond-Stage GambienseHumanAfricanTrypanosomiasis GerardoPriotto1*,Franc?ois Chappuis2,MathieuBastard1,LaurenceFlevaud3,Jean-Franc?oisEtard1,4* 1Epicentre, Paris, France, 2Operational Centre Geneva, Me′decins sans Frontie`res, Geneva University Hospitals, Geneva, Switzerland, 3Operational Centre Barcelona- Athens,Me′decinssansFrontie`res, Barcelona,Spain,4InstitutdeRecherchepourleDe′veloppement/UMI 233,Montpellier,France Abstract Background: Human African trypanosomiasis is fatal without treatment. The long post-treatment follow-up (24 months) requiredtoassesscurecomplicatespatientmanagementandisamajorobstacleinthedevelopmentofnewtherapies.We analyzed individual patient data from 12 programs conducted by Me′decins Sans Frontie`res in Uganda, Sudan, Angola, CentralAfricanRepublic,RepublicofCongoandDemocraticRepublicofCongosearchingforearlyefficacyindicators. Methodology/Principal Findings: Patients analyzed had confirmed second-stage disease with complete follow-up and confirmedoutcome(cureorrelapse),andhadCSFleucocytescounts(CSFLC)performedat6monthspost-treatment.We excludedpatientswithuncertainefficacyoutcome:incompletefollow-up,death,relapsediagnosedwithCSFLCbelow50/ mLandnotrypanosomes.Weanalyzedthe6-monthCSFLCviareceiver-operator-characteristiccurves.Foreachcut-offvalue wecalculatedsensitivity,specificityandlikelihoodratios(LR+andLR2).Weassessedtheassociationoftheoptimalcut-off with the probability of relapsing via random-intercept logistic regression. We also explored two-step (6 and 12 months) compositealgorithmsusingtheCSFLC. Themostaccuratecut-offtopredictoutcomewas10leucocytes/mL(n=1822,76.2%sensitivity,80.4%specificity,3.89 LR+, 0.29 LR2). Multivariate analysis confirmed its association with outcome (odds ratio=17.2). The best algorithm established cure at 6 months with ,=5 leucocytes/mL and relapse with .=50 leucocytes/mL; patients between these valueswerediscriminatedat12monthsbya20leucocytes/mLcut-off(n=2190,8