Reversal of Chloroquine Resistance in Plasmodium falciparum in Gabon: A Phenotype-Genotype Relationship Over the Last 20 Years

Inoue, Juliana; Rodi, Miriam; Bohissou, Francis Emmanuel Towanou; de Carvalho, Lais Pessanha; Lohse, Katharina; Koehne, Erik; Agnandji, Selidji T.; Mombo-Ngoma, Ghyslain; Kremsner, Peter G.; Kreidenweiss, Andrea; Held, Jana

doi:10.3390/ijms27083566

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Reversal of Chloroquine Resistance in Plasmodium falciparum in Gabon: A Phenotype-Genotype Relationship Over the Last 20 Years

by

Juliana Inoue

¹

,

Miriam Rodi

¹,

Francis Emmanuel Towanou Bohissou

^1,2

,

Lais Pessanha de Carvalho

¹

,

Katharina Lohse

¹,

Erik Koehne

^1,3

,

Selidji T. Agnandji

^3,4,

Ghyslain Mombo-Ngoma

^3,5

,

Peter G. Kremsner

^1,3,6,

Andrea Kreidenweiss

^1,3,6

and

Jana Held

^1,3,6,*

¹

Institute of Tropical Medicine Tübingen, University Hospital Tübingen, Wilhelmstraße 27, 72074 Tübingen, Germany

²

Centre de Recherche Entomologique de Cotonou, Cotonou 06 BP 2604, Benin

³

Centre de Recherches Médicales de Lambaréné (CERMEL), Lambaréné BP 242, Gabon

⁴

Institute for Medical Microbiology, University of Münster, 48149 Münster, Germany

⁵

Research Group Drug Implementation, Bernhard Nocht Institute for Tropical Medicine & I. Department of Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany

⁶

German Center for Infection Research (DZIF), Partner Site Tübingen, 72074 Tübingen, Germany

^*

Author to whom correspondence should be addressed.

Int. J. Mol. Sci. 2026, 27(8), 3566; https://doi.org/10.3390/ijms27083566

Submission received: 18 March 2026 / Revised: 8 April 2026 / Accepted: 9 April 2026 / Published: 16 April 2026

(This article belongs to the Special Issue Molecular Research on Parasitic Infection)

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Abstract

The emergence of chloroquine-resistant Plasmodium falciparum in the 1950s posed a global threat to malaria control. Ceasing chloroquine use restored chloroquine-sensitive strains in many African countries. To assess whether chloroquine sensitivity re-emerged in Lambaréné, Gabon, we compiled published and new data on P. falciparum ex vivo chloroquine susceptibility, quantified as half-maximal inhibitory concentration (IC₅₀), from four time points between 2004 and 2024. We then assessed the prevalence of pfcrt and pfmdr1 polymorphisms associated with chloroquine resistance via real-time PCR and Sanger sequencing, respectively, at six different time points between 2009 and 2024. Ex vivo chloroquine susceptibility data revealed a stepwise decrease in the median chloroquine IC₅₀ from 2004 (113.8 nM; IQR: 79.6–163.5 nM, n = 42), 2009 (46.7 nM; IQR: 27.4–76.9 nM, n = 26), and 2017–2018 (15.6 nM; IQR: 6.1–40.9 nM, n = 46) to 2024 (2.1 nM; IQR: 0.8–6.1 nM, n = 39). The chloroquine-sensitive pfcrt haplotype CVMNK increased from 3.6% (1/28) in 2009 to 98.2% (56/57) in 2024, as well as the wild-type pfmdr1 N86 (23.1% (6/16), 2009; 100% (19/19), 2024). Paired molecular and ex vivo analyses revealed an association between IC₅₀ values and CVMNK pfcrt and pfmdr1 N86. Our data provide evidence for the reestablishment of chloroquine-sensitive P. falciparum in Lambaréné, Gabon.

Keywords: chloroquine resistance; Plasmodium falciparum; pfcrt gene; pfmdr1 gene

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MDPI and ACS Style

Inoue, J.; Rodi, M.; Bohissou, F.E.T.; de Carvalho, L.P.; Lohse, K.; Koehne, E.; Agnandji, S.T.; Mombo-Ngoma, G.; Kremsner, P.G.; Kreidenweiss, A.; et al. Reversal of Chloroquine Resistance in Plasmodium falciparum in Gabon: A Phenotype-Genotype Relationship Over the Last 20 Years. Int. J. Mol. Sci. 2026, 27, 3566. https://doi.org/10.3390/ijms27083566

AMA Style

Inoue J, Rodi M, Bohissou FET, de Carvalho LP, Lohse K, Koehne E, Agnandji ST, Mombo-Ngoma G, Kremsner PG, Kreidenweiss A, et al. Reversal of Chloroquine Resistance in Plasmodium falciparum in Gabon: A Phenotype-Genotype Relationship Over the Last 20 Years. International Journal of Molecular Sciences. 2026; 27(8):3566. https://doi.org/10.3390/ijms27083566

Chicago/Turabian Style

Inoue, Juliana, Miriam Rodi, Francis Emmanuel Towanou Bohissou, Lais Pessanha de Carvalho, Katharina Lohse, Erik Koehne, Selidji T. Agnandji, Ghyslain Mombo-Ngoma, Peter G. Kremsner, Andrea Kreidenweiss, and et al. 2026. "Reversal of Chloroquine Resistance in Plasmodium falciparum in Gabon: A Phenotype-Genotype Relationship Over the Last 20 Years" International Journal of Molecular Sciences 27, no. 8: 3566. https://doi.org/10.3390/ijms27083566

APA Style

Inoue, J., Rodi, M., Bohissou, F. E. T., de Carvalho, L. P., Lohse, K., Koehne, E., Agnandji, S. T., Mombo-Ngoma, G., Kremsner, P. G., Kreidenweiss, A., & Held, J. (2026). Reversal of Chloroquine Resistance in Plasmodium falciparum in Gabon: A Phenotype-Genotype Relationship Over the Last 20 Years. International Journal of Molecular Sciences, 27(8), 3566. https://doi.org/10.3390/ijms27083566

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Reversal of Chloroquine Resistance in Plasmodium falciparum in Gabon: A Phenotype-Genotype Relationship Over the Last 20 Years

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