Prévalence des marqueurs moléculaires de résistance de Plasmodium falciparum à la Sulfadoxine-Pyriméthamine et à l’Amodiaquine au début de la chimioprévention du paludisme saisonnier au Togo
Abstract
Objectif: Déterminer la prévalence des marqueurs de résistance de P.falciparum à la Sulfadoxine-Pyriméthamine et à l’Amodiaquine au début de la mise en œuvre de la chimioprévention du paludisme saisonnier (CPS) au Togo. Méthodes: Une enquête transversale conduite dans la région des Savanes, zone éligible, et dans une zone témoin hors de la zone éligible, a porté sur des enfants âgés de 3 à 59 mois, symptomatiques ou non, résidant depuis plus de 6 mois dans les localités tirées. L’analyse moléculaire a recherché les mutations sur les codons 51, 59 et 108 de Pfdhfr, et 437 et 540 de Pfdhps pour la sulfadoxine-pyriméthamine ; ainsi que les mutations sur le codon 76 de Pfcrt et 86 de Pfmdr1 pour l’amodiaquine. Résultats: La prévalence de l’allèle triple mutant Pfdhfr était élevée avec 86,4% en zone CPS et 77,9% en zone non-CPS avec une différence significative (p=0,008). La prévalence de la mutation 437G Pfdhps était élevée dans les deux zones (83,2% et 78,2%). Par contre, celle de la mutation 540E était faible (1,8% et 4,3%). La prévalence de l’allèle double mutant Pfdhps en a été impacté avec 1,4% et 4,3%, et une différence significative (p=0,04). Les prévalences des mutations sur Pfcrt et Pfmdr1 étaient inférieures à la moyenne en Afrique. Conclusion: L’utilisation de sulfadoxine-pyriméthamine et amodiaquine pour la CPS n’était pas compromise. Des données de base de la surveillance moléculaire de la résistance de P.falciparum aux antipaludiques au Togo sont disponibles.
Objective: To determine the prevalence of P.falciparum resistance markers to Sulfadoxine-Pyrimethamine and Amodiaquine at the start of the implementation of seasonal malaria chemoprevention (SMC) in Togo. Methods: A cross-sectional survey conducted in the Savanes region, an eligible area, and in a control area outside the eligible area, focused on children aged 3 to 59 months, symptomatic or not, residing for more than 6 months in the selected localities. Molecular analysis was performed to screen for mutations at codons 51, 59, and 108 of Pfdhfr, and 437 and 540 of Pfdhps for sulfadoxine-pyrimethamine; as well as mutations at codon 76 of Pfcrt and codon 86 of Pfmdr1 for amodiaquine. Results: Triple mutant Pfdhfr allele prevalence was high, 86.4% in SMC area and 77.9% in the non-SMC area, with a significant difference (p=0.008). Prevalence of 437G Pfdhps mutation was high in both areas (83.2% and 78.2%). In contrast, prevalence of 540E mutation was low (1.8% and 4.3%). Double mutant Pfdhps allele prevalence was impacted by this, 1.4% and 4.3%, with a significant difference (p=0.04). Prevalence of mutations in Pfcrt and Pfmdr1 was lower than the average observed in Africa. Conclusion: The use of sulfadoxine-pyrimethamine and amodiaquine for SMC was not compromised. Baseline data from molecular surveillance of P. falciparum resistance to antimalarial drugs in Togo are available.
Downloads
PlumX Statistics
References
Diourte, Y., Djimdé, A., Doumbo, O. K., Sagara, I., Coulibaly, Y., Dicko, A., Diallo, M., Diakité, M., Cortese, J. F. & Plowe, C. V. (1999). Pyrimethamine-sulfadoxine efficacy and selection for mutations in Plasmodium falciparum dihydrofolate reductase and dihydropteroate synthase in Mali. The American journal of tropical medicine and hygiene, 60(3), 475-478. DOI: https://doi.org/10.4269/ajtmh.1999.60.475
Djimdé, A., Doumbo, O. K., Cortese, J. F., Kayentao, K., Doumbo, S., Diourté, Y., Coulibaly, D., Dicko, A., Su, X. Z., Nomura, T., Fidock, D. A., Wellems, T. E. & Plowe, C. V. (2001). A molecular marker for chloroquine-resistant falciparum malaria. New England journal of medicine, 344(4), 257-263. DOI: https://doi.org/10.1056/NEJM200101253440403
Dorkenoo, M.A., Barrette, A., Agbo, Y.M., Bogreau, H., Kutoati, S., Sodahlon, Y. K. & Morgah, K. (2012). Surveillance of the efficacy of artemether-lumefantrine and artesunate-amodiaquine for the treatment of uncomplicated Plasmodium falciparum among children under five in Togo, 2005-2009. Malaria Journal, 11, 338. DOI: https://doi.org/10.1186/1475-2875-11-338
Dorkenoo, A. M., Yehadji, D., Agbo, Y. M., Layibo, Y., Agbeko, F., Adjeloh, P., Yakpa, K., Sossou, E., Awokou, F. & Ringwald, P. (2016). Therapeutic efficacy trial of artemisinin-based combination therapy for the treatment of uncomplicated malaria and investigation of mutations in k13 propeller domain in Togo, 2012–2013. Malaria journal, 15(1), 1-9. DOI: https://doi.org/10.1186/s12936-016-1381-8
Gesase, S., Gosling, R. D., Hashim, R., Ord, R., Naidoo, I., Madebe, R., Mosha, J. F., Joho, A., Mandia, V., Mrema, H., Mapunda, E., Savael, Z., Lemnge, M., Mosha, F. W., Greewood, B., Roper, C. & Chandramohan, D. (2009). High resistance of Plasmodium falciparum to sulphadoxine/pyrimethamine in northern Tanzania and the emergence of dhps resistance mutation at Codon 581. PLoS One, 4(2), e4569. DOI: https://doi.org/10.1371/journal.pone.0004569
Happi, C. T., Gbotosho, G. O., Folarin, O. A., Bolaji, O. M., Sowunmi, A., Kyle, D. E., Milhous, W., Wirth, D. F. & Oduola, A. M. J. (2006). Association between mutations in plasmodium falciparum chloroquine resistance transporter and p. falciparum multidrug resistance 1 genes and in vivo amodiaquine resistance in p. falciparum malaria–infected children in Nigeria. The American journal of tropical medicine and hygiene, 75(1), 155-161. DOI: https://doi.org/10.4269/ajtmh.2006.75.155
Holmgren, G., Gil, J. P., Ferreira, P. M., Veiga, M. I., Obonyo, C. O. & Björkman, A. (2006). Amodiaquine resistant Plasmodium falciparum malaria in vivo is associated with selection of pfcrt 76T and pfmdr1 86Y. Infection, Genetics and Evolution, 6(4), 309-314. DOI: https://doi.org/10.1016/j.meegid.2005.09.001
Hyde, J. E. (2005). Exploring the folate pathway in Plasmodium falciparum. Acta tropica, 94(3), 191-206. DOI: https://doi.org/10.1016/j.actatropica.2005.04.002
Konaté, A. T., Yaro, J. B., Ouédraogo, A. Z., Diarra, A., Gansané, A., Soulama, I., Kangoyé, D. T., Kaboré, Y., Ouédraogo, E., Ouédraogo, A., Tiono, A. B., Ouédraogo, I. N., Chandramohan, D., Cousens, S., Milligan, P. J., Sirima, S. B., Greenwood, B. & Diallo, D. A. (2011). Intermittent preventive treatment of malaria provides substantial protection against malaria in children already protected by an insecticide-treated bednet in Burkina Faso : a randomised, double-blind, placebo-controlled trial. PLoS medicine, 8(2), e1000408. DOI: https://doi.org/10.1371/journal.pmed.1000408
Kublin, J. G., Dzinjalamala, F. K., Kamwendo, D. D., Malkin, E. M., Cortese, J. F., Martino, L. M., Mukadam, R. A. G., Rogerson, S. J., Lescano, A. G., Molyneux, M. E., Winstanley, P. A., Chimpeni, P., Taylor, T. E. & Plowe, C. V. (2002). Molecular markers for failure of sulfadoxine-pyrimethamine and chlorproguanil-dapsone treatment of Plasmodium falciparum malaria. The Journal of infectious diseases, 185(3), 380-388. DOI: https://doi.org/10.1086/338566
Ministère de la Santé, Togo. Mise en œuvre du plan stratégique national 2011-2015 de lutte contre le paludisme : rapport annuel du Programme National de Lutte contre le Paludisme (2013). Ministère de la Santé, Togo.
Naidoo, I. & Roper, C. (2010). Following the path of most resistance: dhps K540E dispersal in African Plasmodium falciparum. Trends in parasitology, 26(9), 447-456. DOI: https://doi.org/10.1016/j.pt.2010.05.001
Naidoo, I. & Roper, C. (2011). Drug resistance maps to guide intermittent preventive treatment of malaria in African infants. Parasitology, 138(12), 1469-1479. DOI: https://doi.org/10.1017/S0031182011000746
Ogouyèmi-Hounto, A., Ndam, N. T., Kinde Gazard, D., d’Almeida, S., Koussihoude, L., Ollo, E., Azagnandji, C., Bello, M., Chippaux, J-P. & Massougbodji, A. (2013). Prevalence of the molecular marker of Plasmodium falciparum resistance to chloroquine and sulphadoxine/pyrimethamine in Benin seven years after the change of malaria treatment policy. Malaria Journal, 12(1), 147. DOI: https://doi.org/10.1186/1475-2875-12-147
Omar, S. A., Adagu, I. S. & Warhurst, D. C. (2001). Can pretreatment screening for dhps and dhfr point mutations in Plasmodium falciparum infections be used to predict sulfadoxine-pyrimethamine treatment failure? Transactions of the Royal Society of Tropical Medicine and Hygiene, 95(3), 315-319. DOI: https://doi.org/10.1016/S0035-9203(01)90250-0
Organisation Mondiale de la Santé. (2010). Recommandation générale de l’OMS sur le traitement préventif intermittent du nourrisson à la sulfadoxine-pyriméthamine pour lutter contre le paludisme à Plasmodium falciparum en Afrique (No. WHO/HTM/GMP/2010.01). Organisation mondiale de la Santé. https://iris.who.int/handle/10665/338711
Plowe, C. V., Cortese, J. F., Djimde, A., Nwanyanwu, O. C., Watkins, W. M., Winstanley, P. A., Estrada-Franco, J. G., Mollinedo, R. E., Avila, J. C., Cespedes, J. L., Carter, J. & Doumbo, O. K. (1997). Mutations in Plasmodium falciparum dihydrofolate reductase and dihydropteroate synthase and epidemiologic patterns of pyrimethamine-sulfadoxine use and resistance. Journal of Infectious Diseases, 176(6), 1590-1596. DOI: https://doi.org/10.1086/514159
Sibley, C. H., Hyde, J. E., Sims, P. F., Plowe, C. V., Kublin, J. G., Mberu, E. K., Cowman, A. F., Winstanley, P. A., Watkins, W. M. & Nzila, A. M. (2001). Pyrimethamine–sulfadoxine resistance in Plasmodium falciparum: what next?. Trends in parasitology, 17(12), 582-588. DOI: https://doi.org/10.1016/S1471-4922(01)02085-2
Staedke, S. G., Sendagire, H., Lamola, S., Kamya, M. R., Dorsey, G. & Rosenthal, P. J. (2004). Relationship between age, molecular markers, and response to sulphadoxine–pyrimethamine treatment in Kampala, Uganda. Tropical Medicine & International Health, 9(5), 624-629. DOI: https://doi.org/10.1111/j.1365-3156.2004.01239.x
Tekete, M., Djimde, A. A., Beavogui, A. H., Maiga, H., Sagara, I., Fofana, B., Ouologuem, D., Dama, S., Kone, A., Dembele, D., Wele, M., Dicko, A. & Doumbo, O. K. (2009). Efficacy of chloroquine, amodiaquine and sulphadoxine-pyrimethamine for the treatment of uncomplicated falciparum malaria: revisiting molecular markers in an area of emerging AQ and SP resistance in Mali. Malaria Journal, 8(1), 34. DOI: https://doi.org/10.1186/1475-2875-8-34
Venkatesan, M., Gadalla, N. B., Stepniewska, K., Dahal, P., Nsanzabana, C., Moriera, C., Price, R. N., Mårtensson, A., Rosenthal, P. J., Dorsey, G., Sutherland, C. J., Guérin, P., Davis, T. M. E., Ménard, D., Adam, I., Ademowo, G., Arze, C., Baliraine, F. N., Berens-Riha, N., Björkman, A., Borrmann, S., Checchi, F., ... & Sibley, C. H. (2014). Polymorphisms in Plasmodium falciparum chloroquine resistance transporter and multidrug resistance 1 genes: parasite risk factors that affect treatment outcomes for P. falciparum malaria after artemether-lumefantrine and artesunate-amodiaquine. The American journal of tropical medicine and hygiene, 91(4), 833. DOI: https://doi.org/10.4269/ajtmh.14-0031
Wang, P., Lee, C. S., Bayoumi, R., Djimde, A., Doumbo, O., Swedberg, G., Dao, L. D., Mshinda, H., Tanner, M., Watkins, W. M., Sims, P. F. & Hyde, J. E. (1997). Resistance to antifolates in Plasmodium falciparum monitored by sequence analysis of dihydropteroate synthetase and dihydrofolate reductase alleles in a large number of field samples of diverse origins. Molecular and biochemical parasitology, 89(2), 161-177. DOI: https://doi.org/10.1016/S0166-6851(97)00114-X
Wang, P., Read, M., Sims, P. F. & Hyde, J. E. (1997). Sulfadoxine resistance in the human malaria parasite Plasmodium falciparum is determined by mutations in dihydropteroate synthetase and an additional factor associated with folate utilization. Molecular microbiology, 23(5), 979-986. DOI: https://doi.org/10.1046/j.1365-2958.1997.2821646.x
World Health Organization, Global Partnership to Roll Back Malaria, World Bank, United Nations Development Programme, African Summit on Roll Back Malaria (2000 : Abuja, Nigeria) et al., (2003). La Déclaration d' Abuja et le plan d' action : extrait du Sommet africain pour faire reculer le paludisme, Abuja, 25 avril 2000 (WHO/CDS/RBM/2000.17). Organisation mondiale de la Santé. https://apps.who.int/iris/handle/10665/67817
World Health Organization (2006). Guidelines for the treatment of Malaria, 1st ed. World Health Organization. https://ec.europa.eu/echo/files/policies/sectoral/health_2006_malaria_treatment_guidelines_who.pdf
World Health Organization (2010) : Global report on antimalarial drug efficacy and drug resistance: 2000-2010.Geneva: World Health Organization.
World Health Organization (2011). World malaria report 2011 https://www.who.int/publications/i/item/9789241564403
World Health Organization (2012). WHO policy recommendation: seasonal malaria chemoprevention (SMC) for plasmodium falciparum malaria control in highly seasonal transmission areas of the Sahel sub-region in Africa. World Health Organization. https://iris.who.int/handle/10665/337978
World Health Organization. Policy brief for the implementation of intermittent preventive treatment of malaria in pregnancy using sulfadoxine-pyrimethamine (IPTp-SP). Geneva, World Health Organization, 2013. https://www.who.int/publications/i/item/WHO-HTM-GMP-2014.4
World Health Organisation (2024). Rapport 2024 sur le paludisme dans le monde. https://cdn.who.int/media/docs/default-source/malaria/world-malaria-reports/world-malaria-report-2024-global-briefing-kit-fre.pdf
Copyright (c) 2026 Yao Mawuenyégan Agbo, Komi Kusiaku, Kossi Alowe, Kokou Messan Afanou, Bakenanmè Lare, Nadiédjoa Kokou Douti

This work is licensed under a Creative Commons Attribution 4.0 International License.


