MSF Scientific Days 2017 Development and external validation of a clinical prognostic score for death in visceral leishmaniasis patients in an area of Ethiopia with a high burden of HIV co-infection Charles Abongomera1,2, Koert Ritmeijer3, Florian Vogt2, Jozefien Buyze2, Zelalem Mekonnen1, Henok Admassu1, Robert Colebunders2, Rezika Mohammed4, Lutgarde Lynen2, Ermias Diro4, Johan van Griensven2 1MSF, Abdurafi, Ethiopia; 2Institute of Tropical Medicine, Antwerp, Belgium; 3MSF, Amsterdam, Netherlands; 4University of Gondar, Gondar, Ethiopia Charles Abongomera, MSF, Development and validation of a clinical prognostic score for death from visceral leishmaniasis

Context Ethiopia is one of the top six countries with high burden of visceral leishmaniasis (VL). 3400–5000 VL cases/year. NW Ethiopia: 20 – 40% VL-HIV co-infected. Migrant workers are most at risk. Charles Abongomera, MSF, Development and validation of a clinical prognostic score for death from visceral leishmaniasis

2004: MSF-Abdurafi health center, NW Ethiopia. High case fatality rates in VL sub groups (617%). Sodium stibogluconate (SSG) - severe adverse events. Liposomal amphotericin B (AmBisome) - efficacious, safe, expensive. Charles Abongomera, MSF, Development and validation of a clinical prognostic score for death from visceral leishmaniasis Charles Abongomera, MSF, Development and validation of a clinical prognostic score for death from visceral leishmaniasis

Rationale and objectives Classification of VL severity and optimal management are poorly defined. CPS: classification of severity => Focused strategies =>  CFR Study objectives To identify predictors of death from VL. To develop and externally validate a CPS for death in VL patients. Charles Abongomera, MSF, Development and validation of a clinical prognostic score for death from visceral leishmaniasis

Methods (1) Setting: Development - Abdurafi health center (MSF), ex. Validation - LRTC (University of Gondar Hospital). Retrospective cohort study. Ethics approval: ITM-Antwerp, IPH-Gondar University ERB’s and permission of OCA medical director. Inclusion criteria: Development cohort-> Jan 2008 - Dec 2013. Ex. validation cohort-> Jan 2011- Dec 2012. Outcome: death or cure. Charles Abongomera, MSF, Development and validation of a clinical prognostic score for death from visceral leishmaniasis

Methods (2) Literature review for predictors of death. Spiegelhalter and Knill-Jones method (adjusted LHR of <0.67 or >1.5 => score). Whole dataset used to develop the score. 5-fold cross validation and external validation. Probability of death and diagnostic accuracy by CPS. Area under the receiver operating characteristic curve (AUROC). Charles Abongomera, MSF, Development and validation of a clinical prognostic score for death from visceral leishmaniasis

Selected patient characteristics Charles Abongomera, MSF, Development and validation of a clinical prognostic score for death from visceral leishmaniasis

Adjusted LHR and score by predictor Charles Abongomera, MSF, Development and validation of a clinical prognostic score for death from visceral leishmaniasis

Probability of death by CPS Charles Abongomera, MSF, Development and validation of a clinical prognostic score for death from visceral leishmaniasis

Diagnostic accuracy at different cut-offs 1Number of patients dead/overall number of VL patients, presented as a percentage. Charles Abongomera, MSF, Development and validation of a clinical prognostic score for death from visceral leishmaniasis

ROC curve summarising CPS performance Charles Abongomera, MSF, Development and validation of a clinical prognostic score for death from visceral leishmaniasis

Organisation of care High risk Charles Abongomera, MSF, Development and validation of a clinical prognostic score for death from visceral leishmaniasis

Intermediate risk Charles Abongomera, MSF, Development and validation of a clinical prognostic score for death from visceral leishmaniasis

Low risk CPS can be used in clinical trials aimed at  mortality, to standardise patients according to risk groups. Charles Abongomera, MSF, Development and validation of a clinical prognostic score for death from visceral leishmaniasis

Limitations Retrospective study. Critical patients may have had more complete data. MSF operational definition of weakness vs. Karnofsky performance. CD4 counts, antiretrovirals => CPS for VL-HIV foreseen. Charles Abongomera, MSF, Development and validation of a clinical prognostic score for death from visceral leishmaniasis

Conclusions/recommendations CPS => good performance in identifying VL patients at high risk of death (classification of VL severity). VL programme management => Focused strategies =>  CFR. Evidence is needed on the impact of the score when applied for such strategies. Validation in other East African countries/areas  VL-HIV. Charles Abongomera, MSF, Development and validation of a clinical prognostic score for death from visceral leishmaniasis

Acknowledgments Staff of Abdurafi health center and LRTC at the University of Gondar, Ethiopia. MSF and Drugs for Neglected Diseases Initiative (DNDi). AfriCoLeish project has supported this work. Charles Abongomera, MSF, Development and validation of a clinical prognostic score for death from visceral leishmaniasis