The Return of Chloroquine-susceptible Plasmodium Falciparum Malaria in Zambia

Overview

Journal Malar J

Publisher Biomed Central

Specialty Tropical Medicine

Date 2016 Dec 7

PMID 27919256

Citations 39

Authors

Sydney Mwanza

Sudhaunshu Joshi

Michael Nambozi

Justin Chileshe

Phidelis Malunga

Jean-Bertin Bukasa Kabuya

Sebastian Hachizovu

Christine Manyando

Modest Mulenga

Miriam Laufer

Affiliations

Soon will be listed here.

Abstract

Background: Plasmodium falciparum resistance to anti-malarial drugs remains a major obstacle to malaria control and elimination. The parasite has developed resistance to every anti-malarial drug introduced for wide-scale treatment. However, the spread of resistance may be reversible. Malawi was the first country to discontinue chloroquine use due to widespread resistance. Within a decade of the removal of drug pressure, the molecular marker of chloroquine-resistant malaria had disappeared and the drug was shown to have excellent clinical efficacy. Many countries have observed decreases in the prevalence of chloroquine resistance with the discontinuation of chloroquine use. In Zambia, chloroquine was used as first-line treatment for uncomplicated malaria until treatment failures led the Ministry of Health to replace it with artemether-lumefantrine in 2003. Specimens from a recent study were analysed to evaluate prevalence of chloroquine-resistant malaria in Nchelenge district a decade after chloroquine use was discontinued.

Methods: Parasite DNA was extracted from dried blood spots collected by finger-prick in pregnant women who were enrolling in a clinical trial. The specimens underwent pyrosequencing to determine the genotype of the P. falciparum chloroquine resistance transporter, the gene that is associated with CQ resistance.

Results: Three-hundred and two specimens were successfully analysed. No chloroquine-resistant genotypes were detected.

Conclusion: The study found the disappearance of chloroquine-resistant malaria after the removal of chloroquine drug pressure. Chloroquine may have a role for malaria prevention or treatment in Zambia and throughout the region in the future.

Citing Articles

Assessing fitness costs in malaria parasites: a comprehensive review and implications for drug resistance management.

Segovia X, Srivastava B, Serrato-Arroyo S, Guerrero A, Huijben S Malar J. 2025; 24(1):65.

PMID: 40025552 PMC: 11871665. DOI: 10.1186/s12936-025-05286-w.

Mapping Antimalarial Drug Resistance in Mozambique: A Systematic Review of Genetic Markers Post-ACT Implementation.

Chaves C, Da Silva C, Salamandane A, Nogueira F Int J Mol Sci. 2025; 25(24.

PMID: 39769406 PMC: 11728251. DOI: 10.3390/ijms252413645.

Setting Up an NGS Sequencing Platform and Monitoring Molecular Markers of Anti-Malarial Drug Resistance in Djibouti.

Papa Mze N, Arreh H, Moussa R, Elmi M, Waiss M, Abdi M Biology (Basel). 2024; 13(11).

PMID: 39596860 PMC: 11592001. DOI: 10.3390/biology13110905.

National genomic profiling of antimalarial resistance in Zambian children participating in the 2018 Malaria Indicator Survey.

Fola A, Ciubotariu I, Dorman J, Mwenda M, Mambwe B, Mulube C medRxiv. 2024; .

PMID: 39148823 PMC: 11326323. DOI: 10.1101/2024.08.05.24311512.

Plasmodium falciparum population dynamics in East Africa and genomic surveillance along the Kenya-Uganda border.

Osborne A, Manko E, Waweru H, Kaneko A, Kita K, Campino S Sci Rep. 2024; 14(1):18051.

PMID: 39103358 PMC: 11300580. DOI: 10.1038/s41598-024-67623-4.

References

Ashley E, Dhorda M, Fairhurst R, Amaratunga C, Lim P, Suon S . Spread of artemisinin resistance in Plasmodium falciparum malaria. N Engl J Med. 2014; 371(5):411-23. PMC: 4143591. DOI: 10.1056/NEJMoa1314981. View

Pekyi D, Ampromfi A, Tinto H, Traore-Coulibaly M, Tahita M, Valea I . Four Artemisinin-Based Treatments in African Pregnant Women with Malaria. N Engl J Med. 2016; 374(10):913-27. DOI: 10.1056/NEJMoa1508606. View

Dondorp A, Nosten F, Yi P, Das D, Phyo A, Tarning J . Artemisinin resistance in Plasmodium falciparum malaria. N Engl J Med. 2009; 361(5):455-67. PMC: 3495232. DOI: 10.1056/NEJMoa0808859. View

Morris U, Xu W, Msellem M, Schwartz A, Abass A, Shakely D . Characterising temporal trends in asymptomatic Plasmodium infections and transporter polymorphisms during transition from high to low transmission in Zanzibar, 2005-2013. Infect Genet Evol. 2015; 33:110-7. PMC: 10445533. DOI: 10.1016/j.meegid.2015.04.018. View

Bloland P, Lackritz E, Kazembe P, Were J, Steketee R, CAMPBELL C . Beyond chloroquine: implications of drug resistance for evaluating malaria therapy efficacy and treatment policy in Africa. J Infect Dis. 1993; 167(4):932-7. DOI: 10.1093/infdis/167.4.932. View

Noedl H, Se Y, Schaecher K, Smith B, Socheat D, Fukuda M . Evidence of artemisinin-resistant malaria in western Cambodia. N Engl J Med. 2008; 359(24):2619-20. DOI: 10.1056/NEJMc0805011. View

Slater H, Griffin J, Ghani A, Okell L . Assessing the potential impact of artemisinin and partner drug resistance in sub-Saharan Africa. Malar J. 2016; 15:10. PMC: 4704433. DOI: 10.1186/s12936-015-1075-7. View

Durand R, Jafari S, Vauzelle J, Delabre J, Jesic Z, Le Bras J . Analysis of pfcrt point mutations and chloroquine susceptibility in isolates of Plasmodium falciparum. Mol Biochem Parasitol. 2001; 114(1):95-102. DOI: 10.1016/s0166-6851(01)00247-x. View

Menard D, Khim N, Beghain J, Adegnika A, Shafiul-Alam M, Amodu O . A Worldwide Map of Plasmodium falciparum K13-Propeller Polymorphisms. N Engl J Med. 2016; 374(25):2453-64. PMC: 4955562. DOI: 10.1056/NEJMoa1513137. View

10.

Frosch A, Laufer M, Mathanga D, Takala-Harrison S, Skarbinski J, Claassen C . Return of widespread chloroquine-sensitive Plasmodium falciparum to Malawi. J Infect Dis. 2014; 210(7):1110-4. PMC: 6281358. DOI: 10.1093/infdis/jiu216. View

11.

Laufer M, Plowe C . Withdrawing antimalarial drugs: impact on parasite resistance and implications for malaria treatment policies. Drug Resist Updat. 2004; 7(4-5):279-88. DOI: 10.1016/j.drup.2004.08.003. View

12.

Golassa L, Kamugisha E, Ishengoma D, Baraka V, Shayo A, Baliraine F . Identification of large variation in pfcrt, pfmdr-1 and pfubp-1 markers in Plasmodium falciparum isolates from Ethiopia and Tanzania. Malar J. 2015; 14:264. PMC: 4495614. DOI: 10.1186/s12936-015-0783-3. View

13.

Ndyomugyenyi R, Magnussen P . Trends in malaria-attributable morbidity and mortality among young children admitted to Ugandan hospitals, for the period 1990-2001. Ann Trop Med Parasitol. 2004; 98(4):315-27. DOI: 10.1179/000349804225003433. View

14.

Mbogo G, Nankoberanyi S, Tukwasibwe S, Baliraine F, Nsobya S, Conrad M . Temporal changes in prevalence of molecular markers mediating antimalarial drug resistance in a high malaria transmission setting in Uganda. Am J Trop Med Hyg. 2014; 91(1):54-61. PMC: 4080569. DOI: 10.4269/ajtmh.13-0647. View

15.

Kublin J, Cortese J, Njunju E, Mukadam R, Wirima J, Kazembe P . Reemergence of chloroquine-sensitive Plasmodium falciparum malaria after cessation of chloroquine use in Malawi. J Infect Dis. 2003; 187(12):1870-5. DOI: 10.1086/375419. View

16.

Laufer M, Takala-Harrison S, Dzinjalamala F, Stine O, Taylor T, Plowe C . Return of chloroquine-susceptible falciparum malaria in Malawi was a reexpansion of diverse susceptible parasites. J Infect Dis. 2010; 202(5):801-8. PMC: 3380613. DOI: 10.1086/655659. View

17.

Sagara I, Oduro A, Mulenga M, Dieng Y, Ogutu B, Tiono A . Efficacy and safety of a combination of azithromycin and chloroquine for the treatment of uncomplicated Plasmodium falciparum malaria in two multi-country randomised clinical trials in African adults. Malar J. 2014; 13:458. PMC: 4364337. DOI: 10.1186/1475-2875-13-458. View

18.

Zucker J, Ruebush 2nd T, Obonyo C, Otieno J, Campbell C . The mortality consequences of the continued use of chloroquine in Africa: experience in Siaya, western Kenya. Am J Trop Med Hyg. 2003; 68(4):386-90. View

19.

Cairns M, Roca-Feltrer A, Garske T, Wilson A, Diallo D, Milligan P . Estimating the potential public health impact of seasonal malaria chemoprevention in African children. Nat Commun. 2012; 3:881. PMC: 3621394. DOI: 10.1038/ncomms1879. View

20.

Lakshmanan V, Bray P, Verdier-Pinard D, Johnson D, Horrocks P, Muhle R . A critical role for PfCRT K76T in Plasmodium falciparum verapamil-reversible chloroquine resistance. EMBO J. 2005; 24(13):2294-305. PMC: 1173140. DOI: 10.1038/sj.emboj.7600681. View