Genetics of Drug Resistance in Parasitology


Through the interaction with IHMT researchers, external guests and autonomous study, at the end of the course, students should:
1. Recognize different areas of interest in the study of the genetics of antiparasitic drug resistance and its relevance.
2. Acquire notions of genetic basis of antiparasitic drug resistance, phenotypic adaptation to the environment and the challenges in the definition of resistance.
3. Identify the main drug resistance strategies and their molecular basis in the context of medical parasitology.
4. To understand, analyze and evaluate the applicability of some methodologies and tools for the identification of genetic markers of drug resistance and their applicability in the monitoring, epidemiology and control of parasites with impact on human health.

General characterization





Responsible teacher

Fátima Nogueira


Weekly - Se a UC for oferecida como opcional, o horário será disponibilizado no 2º semestre

Total - 31

Teaching language

English and Portuguese


Attendance of 2/3 of classes is mandatory


• O'Neill PM, Barton VE, Ward SA. The molecular mechanism of action of artemisinin--the debate continues. Molecules. 2010 Mar 12;15(3):1705-21.
• Witkowski B, Berry A, Benoit-Vical F. Resistance to antimalarial compounds: methods and applications. Drug Resist Updat. 2009 Feb-Apr;12(1-2):42-50.
• O'Brien C, Henrich PP, Passi N, Fidock DA. Recent clinical and molecular insights into emerging artemisinin resistance in Plasmodium falciparum. Curr Opin Infect Dis. 2011 Dec;24(6):570-7.
• Sá JM, Chong JL, Wellems TE. Malaria drug resistance: new observations and developments. Essays Biochem. 2011;51:137-60.
• Witkowski B, Lelièvre J, Barragán MJ, Laurent V, Su XZ, Berry A, Benoit-Vical F. Increased tolerance to artemisinin in Plasmodium falciparum is mediated by a quiescence mechanism. Antimicrob Agents Chemother. 2010 May;54(5):1872-7.
• Hemingway J, Hawkes NJ, McCarroll L, Ranson H. 2004. The molecular basis of insecticide resistance in mosquitoes. Insect Biochem Mol Biol 34: 653-665.
• Soderlund DM, Knipple DC. 2003. The molecular biology of knockdown resistance to pyrethroid insecticides. Insect Biochem Mol Biol 33: 563–577.
• Brogdon WG, McAllister JC. 1998. Insecticide resistance and vector control. Emerg Infect Dis 4: 605-613.
• Exploiting Knowledge on Leishmania Drug Resistance to Support the Quest for New DrugsAya Hefnawy, Maya Berg, Jean-Claude Dujardin, Géraldine De Muylder. Trends in Parasitology, 2017. 33: 162-174.
• Leishmania antimony resistance: what we know what we can learn from the field. Aït-Oudhia K, Gazanion E, Vergnes B, Oury B, Sereno D. Parasitol Res. 2011. 109:1225-32.
• Whole genome sequencing of multiple Leishmania donovani clinical isolates provides insights into population structure and mechanisms of drug resistance. Downing T, Imamura H, Decuypere S, Clark TG, Coombs GH, Cotton JA, Hilley JD, de Doncker S, Maes I, Mottram JC, Quail MA, Rijal S, Sanders M, Schönian G, Stark O, Sundar S, Vanaerschot M, Hertz-Fowler C, Dujardin JC, Berriman M. Genome Res. 2011. 21:2143-56.
• Croft SL, Sundar S, Fairlamb AH. Drug resistance in leishmaniasis. Clin Microbiol Rev. 2006. 19(1):111-26.
• Abbas et al. 2014. Acaricide resistance in cattle ticks and approaches to its management: The state of play. Vet Parasitol. 203:6-20.
• Foil et al. 2004. Factors that influence the prevalence of acaricide resistance and tick-borne Diseases. Vet Parasitol. 125: 163-181.
• Vudriko et al. 2016. Emergence of multi-acaricide resistant Rhipicephalus ticks and its implication on chemical tick control in Uganda. Parasites and Vectors. 9:4.
• Lopez-Arias et al. 2014. Reduced Efficacy of Commercial Acaricides Against Populations of Resistant Cattle Tick Rhipicephalus microplus from Two Municipalities of Antioquia, Colombia. Environmental Health Insights. 8:71.
• Abdel-Hamid, A.H.Z, Rawi, S.M. and Arafa, A. F, 2006. Identification of genetic marker associated with the resistance to Schistosoma mansoni infection using random polymorphic DNA analysis. Mem. Inst. Oswaldo Cruz, 101 (8): 863-868.
• Lockyer, A.E, Jones, C.S, Noble, L.R. and Rollinson, D, 2004. Trematodes and snails: an intimate association. Canadian J. Zool, 82 (2): 251.
• Bowman, D.D. (2012) Heartworms, macrocyclic lactones, and the specter of resistance to prevention in the United States. Parasites and Vectors, 5:138-147.doi:10.1186/1756-3305-5-138.
• Catherine Bourguinat, Alice C.Y. Lee, Regina Lizundia, Byron L. Blagburn,Janice L. Liotta, Marc S. Kraus, Kathy Keller, Christian Epe,Louis Letourneau, Claudia L. Kleinman, Tara Paterson,Elena Carreton Gomez, José Alberto Montoya-Alonso, Hubert Smith,Aron Bhan, Andrew S. Peregrine, James Carmichael, Jason Drake,Rudolf Schenker, Ronald Kaminsky, Dwight D. Bowman,Timothy G. Geary, Roger K. Prichard (2015) Macrocyclic lactone resistance in Dirofilaria immitis: Failure of heartworm preventives and investigation of genetic markers for resistance. Veterinary Parasitology 210, 167–178.
• Committee for Medicinal Products for Veterinary Use (CVMP) (2016) Reflection paper on anthelmintic resistance. Draft
• Kopp SR, Kotze AC, McCarthy JS, Traub RJ and GT Coleman (2008): Pyrantel in small animal 469 medicine: 30 years on. Vet Journal, 178: 177-184.
• Madeira de Carvalho, L.M. (2008) Importância da resistência aos anti-helmínticos a propósito da “Roundtable Nematode Resistance, Atenas, 11-13 de Maio de 2007”. Acta Parasitológica Portuguesa, 15 (1/2): 79-91.
• Madeira de Carvalho, L.M.; Farrim, M.C.; Afonso-Roque, M.M.; Fazendeiro, M.I. (2003) Groups, efficacy and egg reappearance period of commonly used anthelmintics in equine practice in Portugal. 9th International Congress of the European Association for Veterinary Pharmacology and Toxicology, Lisbon, Portugal, 13-18th July 2003. J. Vet. Pharm.Therap., 26, Suppl.1, pp. 237-238.
• Madeira de Carvalho, L.M.; Gillespie, A. T.; Serra, P.M.; Bernardo, F.A.; Farrim, A.P.; Jorge, H.; Agrícola, R.; Barbosa, M.; Fazendeiro, I.M. (2003) Integrated control of horse strongylosis in Portugal – Prospects for the use of the nematode trapping fungus Duddingtonia flagrans associated with anthelmintics. 9th International Congress of the European Association for Veterinary Pharmacology and Toxicology, Lisbon, Portugal, 13-18th July 2003. J. Vet. Pharm. Therap., 26, Suppl.1, pp. 231-232.
• Riggio F, Mannella R, Ariti G and S Perrucci (2013): Intestinal and lung parasites in owned dogs 519 and cats from central Italy. Vet. Parasitol. 193: 78-84.
• Sangster, N.C., 1999. Anthelmintic resistance: past, present and future. International Journal for Parasitology 29, 115–124.
• Kelley JM, Elliott TP, Beddoe T, Anderson G, Skuce P, Spithill TW. Current Threat of Triclabendazole Resistance in Fasciola hepatica. Trends Parasitol. 2016 Jun;32(6):458-469.
• Robles-Pérez D, Martínez-Pérez JM, Rojo-Vázquez FA, Martínez-Valladares M. Screening anthelmintic resistance to triclabendazole in Fasciola hepatica isolated from sheep by means of an egg hatch assay. BMC Vet Res. 2015 Aug 28;11:226.
• Vale N, Gouveia MJ, Rinaldi G, Brindley PJ, Gärtner F, Correia da Costa JM. Praziquantel for Schistosomiasis: Single-Drug Metabolism Revisited, Mode of Action, and Resistance. Antimicrob Agents Chemother. 2017 Apr 24;61(5). pii: e02582-16.
• Nana-Djeunga H, Bourguinat C, Pion SD, Kamgno J, Gardon J, Njiokou F, Boussinesq M, Prichard RK. Single nucleotide polymorphisms in β-tubulin selected in Onchocerca volvulus following repeated ivermectin treatment: possible indication of resistance selection. Mol Biochem Parasitol. 2012 Sep;185(1):10-8.

Teaching method

Teaching of this UC is based on the lecturing method, translated into theoretical classes; In the demonstrative method, in a practical laboratory class; In the active and interrogative methods applied in theoretical-practical classes and in a seminar class. There will also be tutorial sessions to support the autonomous study and preparation of the seminars.

Evaluation method

Student evaluation is based on the students' performance in a written multiple choice test with 30 questions (0.5 values each). The approval in the UC implies: i) the accomplishment of a minimum attendance of 75% of the classes and the achievement of a minimum final classification of 10 values (maximum 20 values) in a written test

Subject matter

I. Introduction to the concept of drug resistance and parasitic infection. Concept of the genomic basis of drug resistance. Concepts of phenotypic adaptation to the environment, resistance to antiparasitic drugs, transport of xenobiotics/drugs in eukaryotes.
II. The oxidative stress-response system enzymes and efflux pumps in response to drugs; using as an example the malaria parasite Plasmodium falciparum.
III. Mechanisms of resistance to insecticides. Define the main mechanisms of resistance and its molecular basis. Concept of resistance vs tolerance. Types of resistance (physiological, behavioral).
IV. Monitoring the occurrence of drug resistance: example Pneumocystis jirovecii.
V. Epidemiological relevance of resistance in drugs used in the treatment of leishmaniasis. Resistance to anthelmintics. Difficulties in the definition of resistance. Resistance genomics in nematodes, trematodes and cestodes. Individual and community consequences. Biomphalaria spp and Schistosoma mansoni: Resistant or susceptible. A host specificity and an infection.
VI. Basic concepts of the tools - metabolomics, proteomics and transcriptomics. Post-genomic tools for the study of drug resistance: Experimental Design; Bioinformatics; Examples of applications.


Programs where the course is taught: