Cutaneous leishmaniasis in Morocco: psychosocial burden and simplified diagnosis Issam BENNIS ISBN n° 978-90-5728-583-7 Legal deposit number D/2018/12.293/11 Cover design by Anita Muys (UA media service) Description of cover photo The cover photo shows a 6-month-old facial lesion of cutaneous leishmaniasis in a 7-year-old child living in the northern part of Morocco. Cutaneous leishmaniasis in Morocco: psychosocial burden and simplified diagnosis Cutane leishmaniase in Marokko: psychosociale belasting en vereenvoudigde diagnose Dissertation submitted for the degree of Doctor of Biomedical Sciences at the University of Antwerp Issam BENNIS Promoters: Co-promoters: Prof. Dr. Jean-Claude Dujardin Prof. Dr. Vincent De Brouwere University of Antwerp Institute of Tropical Medicine Antwerp Institute of Tropical Medicine Antwerp Prof. Dr. Marleen Boelaert Prof. Dr. Hamid Sahibi Institute of Tropical Medicine Antwerp Agricultural and Veterinary Institute Rabat Antwerp – April 17th, 2018 Individual Doctorate Committee: Chair: Prof. Dr. Luc Kestens University of Antwerp, Antwerp, Belgium Members: Prof. Dr. Louis Maes University of Antwerp, Antwerp, Belgium Prof. Dr. Jean-Claude Dujardin University of Antwerp, Antwerp, Belgium Institute of Tropical Medicine, Antwerp, Belgium Prof. Dr. Marleen Boelaert Institute of Tropical Medicine, Antwerp, Belgium External Jury Members: Prof. Dr. François Chappuis Geneva University Hospitals, Geneva, Zwitzerland Dr. José Antonio Ruiz Postigo World Health Organisation, Geneva, Zwitzerland Internal Jury Members: Dr. Edwin Wouters University of Antwerp, Antwerp, Belgium Table of Contents Abbreviations Summary............................................................................................................... 11 Samenvatting ........................................................................................................ 13 CHAPTER 1. General introduction ........................................................................... 15 1. Leishmaniasis, an overview ............................................................................ 17 2. Cutaneous leishmaniasis ................................................................................ 24 2.1 Clinical aspects ......................................................................................... 24 2.2 Diagnosis of cutaneous leishmaniasis ........................................................ 24 2.2.1 Classical methods ............................................................................... 26 2.2.2 Immunological diagnosis .................................................................... 26 2.2.3 Polymerase chain reaction methods ................................................... 27 2.2.4 Identification of Leishmania species ................................................... 28 2.3 Treatment of cutaneous leishmaniasis ...................................................... 28 3. Cutaneous leishmaniasis in Morocco .............................................................. 30 3.1 State of the art of research on CL in Morocco ............................................ 32 3.1.1 Transmission of CL: on host, parasite, and vector ................................ 33 3.1.2 Epidemiological burden ...................................................................... 37 3.1.3 Treatment .......................................................................................... 39 3.1.4 Control strategies ............................................................................... 41 3.2 The CL control policy in Morocco ............................................................... 41 4. Psycho-social burden caused by cutaneous leishmaniasis ................................ 42 5 Thesis outline .................................................................................................. 44 5.1 General objective ..................................................................................... 44 5.2 Specific objectives .................................................................................... 44 5.3 Overview of the thesis, by chapter ............................................................ 45 6. References ..................................................................................................... 50 CHAPTER 2. CONTROL OF CUTANEOUS LEISHMANIASIS CAUSED BY LEISHMANIA MAJOR IN SOUTHEASTERN MOROCCO .................................................................. 65 CHAPTER 3. Psychosocial impact of scars due to cutaneous leishmaniasis on high school students in Errachidia province, Morocco ................................................... 85 CHAPTER 4. Social impact of Cutaneous Leishmaniasis in Southeastern Morocco, A qualitative study. ............................................................................................. 107 CHAPTER 5. Psychosocial burden of localised cutaneous leishmaniasis : a scoping review. ............................................................................................................... 129 CHAPTER 6. Accuracy of a rapid diagnostic test based on antigen detection for the diagnosis of cutaneous leishmaniasis in patients with suggestive skin lesions in Morocco. ............................................................................................................ 157 CHAPTER 7. General discussion ........................................................................... 179 1. Cutaneous leishmaniasis control .................................................................. 181 2. Cutaneous leishmaniasis social representations and psychological suffering . 185 3. Cutaneous leishmaniasis clinical management ............................................. 187 4. Recommendations and conclusion ............................................................... 190 Supporting information ....................................................................................... 201 Acknowledgements ............................................................................................ 247 Abbreviations ACL Anthroponotic cutaneous leishmaniasis AIDS Acquired immunodeficiency syndrome CBI Cutaneous body image CIMVC Committee of integrated management of vector control CL Cutaneous leishmaniasis DALY Disability-Adjusted Life Year DAT Direct agglutination test DCL Diffuse cutaneous leishmaniasis DELM Direction de l’Epidémiologie et de la Lutte contre les Maladies (Directorate of Epidemiology and Disease Control) DLQI Dermatology life quality index DNA Deoxyribonucleic acid ELISA Enzyme-linked immunosorbent assay EMR Eastern mediterranian region FGD Focus group discussion Fig Figure FR Female respondent from Rissani area FT Female respondent from Tinejdad area GBD Global burden of disease HCP High Commission for Planning HIV Human immunodeficiency virus HSP70 Heat shock protein 70 IFAT Immunofluorescence antibody test IFN Interferon IPM Institut Pasteur du Maroc IRS Indoor residual spraying ITN Insecticide-treated net ITS1 Internal transcribed spacer KAP Knowledge, Attitudes, and Practices L. Leishmania LAMP Loop-Mediated Isothermal Amplification LCL Localised cutaneous leishmaniasis LLIN Long-lasting insecticide-treated net LMIC Low and middle-income countries LST Leishmanin Skin Test MCL Mucocutaneous leishmaniasis MLEE Multi locus enzyme electrophoresis MLMT Multilocus microsatellite typing MoA Ministry of Agriculture MoH Ministry of Health MR Male respondent from Rissani area MT Male respondent from Tinejdad area NIH National Institute of Hygiene NNN Novy-MacNeal-Nicolle medium NPV Negative Predictive Value NTD Neglected tropical diseases OR Odds ratio PCR Polymerase chain reaction Ph. Phlebotomus PKDL Post Kala-Azar dermal leishmaniasis PPV Positive predictive value QoL Quality of life RDT Rapid diagnostic test RFLP Restriction Fragment Length Polymorphism Se Sensitivity Sp Specificity TB Tuberculosis VL Visceral leishmaniasis WHO World Health Organisation YLD Years Lost due to Disability YLL Years of life lost due to premature mortality ZCL Zoonotic cutaneous leishmaniasis Summary Introduction Cutaneous leishmaniasis (CL) is a neglected tropical disease (NTD) affecting more than one million persons worldwide. In Morocco, reporting over the past decade on average more than 4000 cases per year, CL is considered a public health problem. CL is mainly poverty-related in Morocco. The social representations of CL were never explored, though efficient control requires understanding of people’s perception and community involvement. To fill this gap, and to facilitate early diagnosis of CL, our research aimed to document the psychosocial burden of CL in these regions, and to assess a new diagnostic tool for CL that is appropriate for use in remote endemic areas. Methods We first described a major outbreak of CL that took place between 2010 to 2012 in Errachidia province. We documented the intersectoral response measures including environmental management and reservoir control. The reservoir of L. major, a rodent, Meriones shawi, was targeted using strychnine-poisoned wheat baits. The second part of the thesis documents social representations of CL in Southeastern Morocco, in both L. major and L. tropica areas. In 2015, we conducted qualitative research in a group of high school students living in L. major areas to study their perception of CL. Furthermore, we conducted focus group discussions on CL perception and its psychosocial burden in the adult population in Errachidia and Tinghir provinces. We related our findings on psychosocial burden to those