Background and Objective: In 2005, Chad, like several other WHO countries, withdrew chloroquine as a first-line treatment for Plasmodium falciparum malaria in response to WHO recommendations related to the reason for the increase in treatment failures and the global spread of chloroquine resistance. Artemisinin-based combination therapy (ACTs), Artemether-lumefantrine, has replaced chloroquine as the first-choice treatment for malaria. The present study assessed pfcrt polymorphism in Plasmodium falciparum isolates in Massakory. Methodology and Results: Blood samples for PCR analysis were collected on Whatman 3MM filter paper in Massakory during a therapeutic efficacy study (TES) conducted from December 14, 2019 to March 14, 2020. Genomic DNA was extracted from 113 dried blood spots with the QIAamp DNA Micro Kit (Qiagen, Valencia, CA) as per manufacturer’s protocol and amplified by nested-PCR with pfcrt specific primer. The amplification products were revealed by electrophoresis on 2% agarose gel and then sequenced according to Sanger method. A total of 71 sequences were readable. The pfcrt analysis showed that of the 71 readable sequences, high mutation prevalence: 66 (92.96%) IET, 2 (4.22%) IDT and 3 (4.22%) MNK wild pfcrt isolates. Conclusion: These results challenge the highest health authorities in the country. The government, through the Ministry of Public Health and National Solidarity and the National Malaria Control Program, must raise awareness for the effective withdrawal of chloroquine. This action will promote on the one hand the re-emergence of parasites sensitive to chloroquine, and on the other hand make possible the reintroduction of chloroquine in the treatment of simple malaria after the suppression of drug pressure.
Published in | American Journal of BioScience (Volume 10, Issue 1) |
DOI | 10.11648/j.ajbio.20221001.14 |
Page(s) | 24-30 |
Creative Commons |
This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited. |
Copyright |
Copyright © The Author(s), 2022. Published by Science Publishing Group |
Malaria, pfcrt, Chloroquine, Plasmodium falciparum, Massakory, Chad
[1] | World Health Organization., (2019). World malaria report 2019. |
[2] | Noedl, H., Se, Y., Schaecher, K., Smith, B. L., Socheat, D., & Fukuda, M. M. (2008). Evidence of Artemisinin-Resistant Malaria in Western Cambodia. New England Journal of Medicine, 359 (24), 2619–2620. |
[3] | Ashley, E. A., Dhorda, M., Fairhurst, R. M., Amaratunga, C., Lim, P., Suon, S., Sreng, S., Anderson, J. M., Mao, S., Sam, B., Sopha, C., Chuor, C. M., Nguon, C., Sovannaroth, S., Pukrittayakamee, S., Jittamala, P., Chotivanich, K., Chutasmit, K., Suchatsoonthorn, C., Runcharoen, R., … Tracking Resistance to Artemisinin Collaboration (TRAC) (2014). Spread of artemisinin resistance in Plasmodium falciparum malaria. The New England journal of medicine, 371 (5), 411–423. |
[4] | Menard, D., & Dondorp, A. (2017). Antimalarial Drug Resistance: A Threat to Malaria Elimination. Cold Spring Harbor perspectives in medicine, 7 (7), a025619. |
[5] | Leang R., Bouth D. M., Song L., Tarning J., Char C., Kim S.,., 2015.- Evidence of falciparum malaria multidrug resistance to artemisinin and piperaquine in western Cambodia : dihydroartemisinin-piperaquine open- label multicenter clinical assessment. Antimicrobial agents and chemotherapy 59, 4719-4726. |
[6] | Takala-Harrison S, Jacob CG, Arze C, Cummings MP, Silva JC, Dondorp AM, Fukuda MM, Hien TT, Mayxay M, Noedl H, Nosten F, Kyaw MP, Nhien NT, Imwong M, Bethell D, Se Y, Lon C, Tyner SD, Saunders DL, Ariey F, Mercereau-Puijalon O, Menard D, Newton PN, Khanthavong M, Hongvanthong B, Starzengruber P, Fuehrer HP, Swoboda P, Khan WA, Phyo AP, Nyunt MM, Nyunt MH, Brown TS, Adams M, Pepin CS, Bailey J, Tan JC, Ferdig MT, Clark TG, Miotto O, MacInnis B, Kwiatkowski DP, White NJ, Ringwald P, Plowe CV (2015). Independent emergence of artemisinin resistance mutations among Plasmodium falciparum in Southeast Asia. Journal of Infectious Diseases, 211: 670-9. |
[7] | Souleymane ISSA M, Clément KH, Denis MM, et al. (2017) Therapeutic Efficacy of Artesunate-Amodiaquine and Polymorphism of Plasmodium falciparum k13-Propeller Gene in Pala (Tchad). Int J Open Access Clin Trials 1 (1): 1. |
[8] | Issa M., 2018. Efficacité thérapeutique de l’association artésunateamodiaquine et polymorphisme des gènes dihydrofolate réductase, dihydroptéroate synthétase et kelch 13 propeller à Pala (République du Tchad). Parasitology. University Félix Houphouët-Boigny (Abidjan, Côte d'Ivoire), 180P. |
[9] | Okech B. A., Existe A., Romain J. R., Memnon G., Victor Y. Saint, Rochars M. B. De, et al., 2015.- Therapeutic Efficacy of Chloroquine for the Treatment of Uncomplicated Plasmodium falciparum in Haiti after Many Decades of its Use, The American journal of tropical medicine and hygiene, 92 (3), 541–545. |
[10] | Amaratunga C., Neal A. T. & Fairhurst R. M., 2014.- Flow cytometry-based analysis of artemisinin-resistant Plasmodium falciparum in the ring-stage survival assay. Antimicrobial Agents and Chemotherapy, 58: 4938–4940. |
[11] | Lehane A. M. & Kirk K., 2010.- Efflux of a range of antimalarial drugs and “chloroquine resistance reversers” from the digestive vacuole in malaria parasites with mutant PfCRT. Molecular Microbiology, 77: 1039–1051. |
[12] | Fidock DA, Nomura T, Talley AK, Cooper RA, Dzekunov SM, Ferdig MT, Ursos LM, Sihdu AB, Naude B, Deitsch KW, Su X, Wootton JC, Roepe PD, Wellems TE. (2000). Mutations in the P. falciparum digestive vacuole transmembrane protein Pfcrt and evidence for their role in chloroquine resistance. Molecular Cell, 6, 861-871. |
[13] | Singh Sidhu A. B., Verdier-Pinard D. & Fidock D. A., 2002.- Chloroquine resistance in Plasmodium falciparum malaria parasites conferred by pfcrt mutations. Science, 298: 210–213. |
[14] | Miotto O., Amato R., Ashley E. A., Macinnis B., Dhorda M., Imwong M., et al., 2015. HHS Public Access, 47: 226–234. |
[15] | Fidock D. A., Ecker A. & Lehane A. M., 2012.- pfcrt and its role in antimalarial drug resistance, Trends in parasitology, 28 (11), 504–514. |
[16] | Venkatesan M, Alifrangis M, Roper C, Plowe CV (2013). Monitoring antifolate resistance in intermittent preventive therapy for malaria. Trends in Parasitology, 29: 497-504. |
[17] | Mahamat Moussa Hasssane Taisso, Issa Mahamat Souleyme, Hamit Mahamat Alio, …, David Koffi, Offianan André Toure, Djaman Alico Joseph. (2021). Effectiveness and tolerability of the ASAQ versus AL association in Children 6-59 months for the treatement of uncomplicated P. falciparum malaria in Massakory (CHAD). AJBLS; 9 (5): 259-266. |
[18] | Sondo P., Bihoun B., Kabore B., Tahita M. C., Derra K., Rouamba T., et al., (2021).- mutations des gènes de résistance Pfcrt et Pfmdr1 dans la zone de Nanoro, Burkina Faso, Malaria journal, 1–9. |
[19] | Kublin J. G., Cortese J. F., Njunju E. M., Mukadam R. A., Wirima J. J. & Kazembe P. N., (2003).- Reemergence of chloroquine-sensitive P. falciparum malaria after cessation of chloroquine use in Malawi. J Infect Dis, 187: 1870-5. |
[20] | Ross L. S., Dhingra S. K., Mok S., Yeo T., Wicht K. J., Kümpornsin K., et al., (2018). Emerging Southeast Asian PfCRT mutations confer Plasmodium falciparum resistance to the fi rst-line. Nature Communications, 25–28. |
[21] | Mwanza S., Joshi S., Nambozi M., Chileshe J., Malunga P., Bertin J., et al., (2016).- The return of chloroquine - susceptible Plasmodium falciparum malaria in Zambia. Malaria Journal, 76: 1–6. |
[22] | Mekonnen S. K., Aseffa A., Berhe N., Teklehaymanot T., Clouse R. M., Gebru T., et al., (2014). Return of chloroquine-sensitive Plasmodium falciparum parasites and emergence of chloroquine-resistant Plasmodium vivax in Ethiopia, Malar J.; 13: 244. |
[23] | Kiarie W. C., Wangai L., Agola E., Kimani F. T. & Hungu C., (2015).- Chloroquine sensitivity : diminished prevalence of chloroquine - resistant gene marker pfcrt - 76 13 years after cessation of chloroquine use in Msambweni, Kenya. Malaria Journal, 1–7. |
[24] | Ikegbunam M. N., Nkonganyi C. N., Thomas B. N., Esimone C. O., Velavan T. P. & Ojurongbe O., (2019).- Analysis of Plasmodium falciparum Pfcrt and Pfmdr1 genes in parasite isolates from asymptomatic individuals in Southeast Nigeria 11 years after withdrawal of chloroquine. Malaria Journal, 1–7. |
[25] | Oladipo O. O., Wellington O. A. & Sutherland C. J., (2015).- Persistence of chloroquine-resistant haplotypes of Plasmodium falciparum in children with uncomplicated Malaria in Lagos, Nigeria, four years after change of chloroquine as first-line antimalarial medicine. Diagnostic pathology, 10, 41. |
[26] | Djaman J, Ahibo H, Yapi FH, Yapi FH, Bla BK, Ouattara L; Yawo W, N’guessan JD, Yapo A, Mazabraud A (2010). Molecular monitoring of falciparum malaria isolate in côte d’Ivoire: genetic markers (dhfr-ts, dhps, pfcrt, pfmdr-1) for antimalarial-drugs résistance. European Journal of Scientific Research, 40, 461- 470. |
[27] | Dagnogo O., Ako A. B., Bla K. B., Dago D. N., Coulibaly N. D., Coulibaly B., et al., (2020). Assessing the polymorphism of DHFR gene from Plasmodium falciparum in the south of Cte dIvoire. African Journal of Microbiology Research, 14: 158–165. |
[28] | Rovira-Graells N., Gupta A. P., Planet E., Crowley V. M., Mok S., Pouplana L. R. De, et al., (2012).- Transcriptional variation in the malaria parasite Plasmodium falciparum. Genome Research, 22: 925–938. |
[29] | Nsango S. E., Abate L., Thoma M., Pompon J., Fraiture M., Rademacher A., et al., (2012).- Genetic clonality of Plasmodium falciparum affects the outcome of infection in Anopheles gambiae. International journal for parasitology, 42: 589–595. |
[30] | Snounou G., Viriyakosol S., Zhu X., Jarra W., Pinheiro L., Rosario V. do, et al., (1993). High sensitivity of detection of human malaria parasites by the use of nested polymerase chain reaction. Molecular and biochemical parasitology, 61: 315–320. |
APA Style
Mahamat Moussa Hassane Taïsso, Ako Aristide Berenger, Issa Mahamat Souleymane, Koui Stéphane Tossea, Kouman Kouamé Bouatini Angelo, et al. (2022). Genetic Polymorphisms in Plasmodium falciparum Chloroquine Resistance Gene, pfcrt in Massakory (Chad). American Journal of BioScience, 10(1), 24-30. https://doi.org/10.11648/j.ajbio.20221001.14
ACS Style
Mahamat Moussa Hassane Taïsso; Ako Aristide Berenger; Issa Mahamat Souleymane; Koui Stéphane Tossea; Kouman Kouamé Bouatini Angelo, et al. Genetic Polymorphisms in Plasmodium falciparum Chloroquine Resistance Gene, pfcrt in Massakory (Chad). Am. J. BioScience 2022, 10(1), 24-30. doi: 10.11648/j.ajbio.20221001.14
AMA Style
Mahamat Moussa Hassane Taïsso, Ako Aristide Berenger, Issa Mahamat Souleymane, Koui Stéphane Tossea, Kouman Kouamé Bouatini Angelo, et al. Genetic Polymorphisms in Plasmodium falciparum Chloroquine Resistance Gene, pfcrt in Massakory (Chad). Am J BioScience. 2022;10(1):24-30. doi: 10.11648/j.ajbio.20221001.14
@article{10.11648/j.ajbio.20221001.14, author = {Mahamat Moussa Hassane Taïsso and Ako Aristide Berenger and Issa Mahamat Souleymane and Koui Stéphane Tossea and Kouman Kouamé Bouatini Angelo and Hamit Mahamat Alio and Mahamat Saleh Issakha Diar and Djiddi Ali Sougoudi and Djimadoum Mbanga and Pascal Ringwald and Djimrassengarh Honoré and Issa Ali Haggar and Hassoumi Manah and Hassan Ahmat Mihedi and N’garadoum Olivier and Brahim Boy Otchom and David Koffi and Dosso Mireille and Djaman Allico Joseph and Offianan André Touré}, title = {Genetic Polymorphisms in Plasmodium falciparum Chloroquine Resistance Gene, pfcrt in Massakory (Chad)}, journal = {American Journal of BioScience}, volume = {10}, number = {1}, pages = {24-30}, doi = {10.11648/j.ajbio.20221001.14}, url = {https://doi.org/10.11648/j.ajbio.20221001.14}, eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ajbio.20221001.14}, abstract = {Background and Objective: In 2005, Chad, like several other WHO countries, withdrew chloroquine as a first-line treatment for Plasmodium falciparum malaria in response to WHO recommendations related to the reason for the increase in treatment failures and the global spread of chloroquine resistance. Artemisinin-based combination therapy (ACTs), Artemether-lumefantrine, has replaced chloroquine as the first-choice treatment for malaria. The present study assessed pfcrt polymorphism in Plasmodium falciparum isolates in Massakory. Methodology and Results: Blood samples for PCR analysis were collected on Whatman 3MM filter paper in Massakory during a therapeutic efficacy study (TES) conducted from December 14, 2019 to March 14, 2020. Genomic DNA was extracted from 113 dried blood spots with the QIAamp DNA Micro Kit (Qiagen, Valencia, CA) as per manufacturer’s protocol and amplified by nested-PCR with pfcrt specific primer. The amplification products were revealed by electrophoresis on 2% agarose gel and then sequenced according to Sanger method. A total of 71 sequences were readable. The pfcrt analysis showed that of the 71 readable sequences, high mutation prevalence: 66 (92.96%) IET, 2 (4.22%) IDT and 3 (4.22%) MNK wild pfcrt isolates. Conclusion: These results challenge the highest health authorities in the country. The government, through the Ministry of Public Health and National Solidarity and the National Malaria Control Program, must raise awareness for the effective withdrawal of chloroquine. This action will promote on the one hand the re-emergence of parasites sensitive to chloroquine, and on the other hand make possible the reintroduction of chloroquine in the treatment of simple malaria after the suppression of drug pressure.}, year = {2022} }
TY - JOUR T1 - Genetic Polymorphisms in Plasmodium falciparum Chloroquine Resistance Gene, pfcrt in Massakory (Chad) AU - Mahamat Moussa Hassane Taïsso AU - Ako Aristide Berenger AU - Issa Mahamat Souleymane AU - Koui Stéphane Tossea AU - Kouman Kouamé Bouatini Angelo AU - Hamit Mahamat Alio AU - Mahamat Saleh Issakha Diar AU - Djiddi Ali Sougoudi AU - Djimadoum Mbanga AU - Pascal Ringwald AU - Djimrassengarh Honoré AU - Issa Ali Haggar AU - Hassoumi Manah AU - Hassan Ahmat Mihedi AU - N’garadoum Olivier AU - Brahim Boy Otchom AU - David Koffi AU - Dosso Mireille AU - Djaman Allico Joseph AU - Offianan André Touré Y1 - 2022/01/15 PY - 2022 N1 - https://doi.org/10.11648/j.ajbio.20221001.14 DO - 10.11648/j.ajbio.20221001.14 T2 - American Journal of BioScience JF - American Journal of BioScience JO - American Journal of BioScience SP - 24 EP - 30 PB - Science Publishing Group SN - 2330-0167 UR - https://doi.org/10.11648/j.ajbio.20221001.14 AB - Background and Objective: In 2005, Chad, like several other WHO countries, withdrew chloroquine as a first-line treatment for Plasmodium falciparum malaria in response to WHO recommendations related to the reason for the increase in treatment failures and the global spread of chloroquine resistance. Artemisinin-based combination therapy (ACTs), Artemether-lumefantrine, has replaced chloroquine as the first-choice treatment for malaria. The present study assessed pfcrt polymorphism in Plasmodium falciparum isolates in Massakory. Methodology and Results: Blood samples for PCR analysis were collected on Whatman 3MM filter paper in Massakory during a therapeutic efficacy study (TES) conducted from December 14, 2019 to March 14, 2020. Genomic DNA was extracted from 113 dried blood spots with the QIAamp DNA Micro Kit (Qiagen, Valencia, CA) as per manufacturer’s protocol and amplified by nested-PCR with pfcrt specific primer. The amplification products were revealed by electrophoresis on 2% agarose gel and then sequenced according to Sanger method. A total of 71 sequences were readable. The pfcrt analysis showed that of the 71 readable sequences, high mutation prevalence: 66 (92.96%) IET, 2 (4.22%) IDT and 3 (4.22%) MNK wild pfcrt isolates. Conclusion: These results challenge the highest health authorities in the country. The government, through the Ministry of Public Health and National Solidarity and the National Malaria Control Program, must raise awareness for the effective withdrawal of chloroquine. This action will promote on the one hand the re-emergence of parasites sensitive to chloroquine, and on the other hand make possible the reintroduction of chloroquine in the treatment of simple malaria after the suppression of drug pressure. VL - 10 IS - 1 ER -